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INTRODUCTION
As pointed out in the first chapter of this volume, inhalation therapy is not new!
Granted, the drugs delivered to the lungs by this method, the propellants, and the
methods themselves are undoubtedly new and constantly improving, but let’s ad-
mit it: the basic principles were established a thousand years ago.
Asthma is certainly one of the diseases, if not the disease, that has bene-
fited most from this therapeutic approach.
In the nineteenth century, one of the “Renaissance men” in the field of
asthma therapy was Henry Hyde Salter, a Fellow of the Royal College of Physi-
cians and a physician at Charing Cross Hospital. He was a strong advocate of in-
halation therapy but, at least by today’s standards, his remedies were horrifying.
Indeed, one was tobacco!
That may be hard to believe, but just read the following: “For tobacco to
cure asthma, as a depressant, it must produce collapse; as a sedative it merely
produces that confusing and tranquilizing condition with which smokers are so
familiar.” And the story goes on, stating that even children may be cured with to-
bacco, but “in carefully measured quantities.”
In his book On Asthma: Its Pathology and Treatment, Salter suggests
many other remedies for the treatment of asthma.
The point of all this is that inhalation therapy has long been recognized as
iii
iv Introduction
a treatment (not cure) of asthma. Of course, today we use pharmacological

agents that are certainly more effective. Asthma is a disease that can be con-
trolled, undoubtedly because of the inhalation administration of the many avail-
able drugs.
Since its beginning, the Lung Biology in Health and Disease series of
monographs has recognized the importance of asthma and, at the same time, of
finding better ways to administer medications for this disease and other condi-
tions as well. This has led to the publication of many volumes on inhalation ther-
apy, covering the methodology and the choice of medications as well.
Drug Delivery to the Lung is a different and timely addition to the se-
ries. As the editors point out in their preface, it is “aimed at clinicians, nurses,
and respiratory therapists interested in the role of aerosol delivery for optimal
management of lung disease.” The beneficiaries of this interest will unques-
tionably be the patients.
I am grateful to the editors and the authors for this major contribution to
the series. The series gains immeasurably from the opportunity to present this
volume to its readership.
Claude Lenfant, M.D.

Bathesda, Maryland
PREFACE
Aerosolized delivery of drugs to the lungs has dramatically improved the treat-
ment of a variety of respiratory diseases. For example, bronchodilator and anti-
inflammatory aerosol medications are the cornerstone of asthma treatment;
antibiotics, DNase, and hypertonic saline are established treatment options in
cystic fibrosis; and nebulized adrenaline and steroids have been used to treat
croup. There is great interest in using the lungs as a portal of entry for systemic
drug therapy. Measles vaccination has been successfully administered via the in-
haled route and the possibility of diabetics inhaling as opposed to injecting in-
sulin is becoming a reality.
Aerosol drug delivery allows treatment to be targeted to the lower airways
and total systemic exposure to be reduced. The device chosen has a major impact
on aerosol delivery, and it should be considered an integral part of any prescription
or drug approval. To date, this is rarely reflected in treatment guidelines for condi-
tions such as asthma and cystic fibrosis, nor in day-to-day clinical practice or drug
labeling. Inconsistent terminology, variations in study methodology and design,
and the absence of guidelines have all led to confusion among practitioners.
Device development and documentation are driven by many different
needs. For patients, important factors include device size, simplicity, irritants,
taste and odors, and interactive features. Such factors impact on compliance,
which is the main hindrance for effectiveness of aerosol treatment. The needs of
the patient change significantly with age. On the other hand, clinicians require
v
vi Preface
knowledge of the fraction of drug likely to reach the lungs when different deliv-
ery devices are used for patients of different ages. Finally, health regulators tend
to emphasize only in vitro reproducibility. The choice of drug defines the need
for accurate estimation of drug delivery; for example, less accurate dosing of
ß2-agonists is acceptable due to their wide therapeutic index. Steroids and in-
sulin, with narrower therapeutic indices, require more accurate drug delivery.
Impact on the environment is an important concern, and risk of exposure of
caregivers should be considered. Efficient devices may be a priority since they
reduce the loss of drug, which improves safety of treatment as well as cost ef-
fectiveness. Such a multitude of needs determines the development, documen-
tation, and, eventually, choice of device.
Aerosol treatment is maturing technically with recent advances in the un-
derstanding of lung dose and major innovations in device technology. If the im-
portant knowledge gained within this area is to have an impact on the
management of our patients, it is mandatory that aerosol standards and principles
be clearly communicated to the health professional. With this aim, a group of
leading experts joined together to develop a milestone publication on the state-
of-the-art knowledge in the area of aerosol treatment. This volume has compiled
their very comprehensive knowledge into an easily readable text with an empha-
sis on clinical implications.
This book is intended for clinicians, nurses, and respiratory therapists in-
terested in the role of aerosol delivery for optimal management of lung diseases.
The content was inspired by a debate between the authors, with the editors serv-
ing as referees. This process was fertilized by a workshop in the spring of 1999,
which defined the general principles and emphasized clinical relevance to the
practitioner. The practical implications of the issues communicated have been
strongly emphasized. Therefore, we hope this book will act as a bridge between
basic aerosol science and good clinical practice in the treatment of lung diseases.
This meeting and the resulting book have been made possible through an
educational grant from AstraZeneca. We wish to express our gratitude to the edi-
tor of this series, Dr. Claude Lenfant, for his interest and support.
Hans Bisgaard
Chris O’Callaghan
Gerald C. Smaldone
CONTRIBUTORS
Jacob Anhøj, M.D. Department of Pediatrics, Copenhagen University Hospi-

tal, Rigshospitalet, Copenhagen, Denmark
Hans Bisgaard, M.D., Ph.D. Professor of Pediatrics, Copenhagen University

Hospital, Rigshospitalet, Copenhagen, Denmark
Lars Borgström, Ph.D. Senior Experimental Medicine Advisor, AstraZeneca

R&D, Lund, and Uppsala University, Uppsala, Sweden
Andy Clark, Ph.D. Inhale Therapeutics Systems, San Carlos, California
John H. Dennis, Ph.D., M.Sc., B.Scl, M.B.I.O.H., Dip Occ Hyg. Senior Lec-
turer, Department of Environmental Science, University of Bradford, Bradford,
West Yorkshire, England
Eric Derom, M.D., Ph.D. Professor, Department of Respiratory Diseases,

Ghent University Hospital, Ghent, Belgium
vii
viii Contributors
Myrna B. Dolovich, P.Eng. Associate Clinical Professor, Department of Med-

icine, McMaster University, Hamilton, Ontario, Canada
Mark L. Everard, M.B., Ch.B., F.R.C.P.C.H., D.M. Department of Respira-

tory Medicine, Sheffield Children’s Hospital, Sheffield, England
Joachim Heyder, Ph.D. Professor and Director, Institute for Inhalation Biol-
ogy, GSF–National Research Center for Environment and Health, Munich, Ger-
many
Alison A. Hislop, Ph.D. Reader, Developmental Vascular Biology, Institute of

Child Health, University College, London, England
Michael E. Hyland, Ph.D. Professor of Health Psychology, University of Ply-

mouth, Plymouth, England
Beth L. Laube, Ph.D. Associate Professor, Department of Pediatrics, Johns

Hopkins University School of Medicine, Baltimore, Maryland
Peter N. LeSouef, M.D., M.R.C.P.(UK), F.R.A.C.P. Professor and Head, De-

partment of Paediatrics, University of Western Australia, Perth, Australia
Ola Nerbrink, Lic. Eng., Ph.D. (MD) Associate Principal Scientist, As-
traZeneca R&D, Lund, Sweden
Chris O’Callaghan, B.Med.Sci., B.M., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D.,

D.M. Professor of Paediatrics, Department of Child Health, and Institute of
Lung Health, University of Leicester, Leicester, England
Martyn R. Partridge, M.D., F.R.C.P. Chest Clinic, Whipps Cross University

Hospital, London, England
Søren Pedersen, M.D., Ph.D. Professor, University of Southern Denmark,

Odense, Denmark, and Adjunct Professor, McMaster University, Hamilton, On-
tario, Canada
Cynthia S. Rand, Ph.D. Associate Professor, Department of Medicine, The

Johns Hopkins School of Medicine, Baltimore, Maryland
Gerald C. Smaldone, M.D., Ph.D. Professor of Medicine, Physiology, and

Biophysics, and Chief, Pulmonary/Critical Care Division, Department of Medi-
cine, State University of New York, Stony Brook, New York
Contributors ix
Janet Stocks, Ph.D. Professor of Respiratory Medicine, Portex Unit, Institute

of Child Health, University College, London, England
Magnus U. Svartengren, M.D., Ph.D. Associate Professor, Department of

Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
Lars Thorsson, Ph.D. Experimental Medicine, AstraZeneca R&D, Lund,

Sweden
Mika T. Vidgren, Ph.D. Professor, Department of Pharmaceutics, University

of Kuopio, Kuopio, Finland
Johannes H. Wildhaber, M.D., Ph.D. Department of Respiratory Medicine,

University Children’s Hospital, Zurich, Switzerland
Ashley A. Woodcock, B.Sc., M.D., F.R.C.P. Professor of Respiratory Medi-

cine, North West Lung Centre, Wythenshawe Hospital, Manchester, England
Paul Wright AstraZeneca R&D, Charnwood, Loughborough, England
Pieter Zanen, M.D., Ph.D. Department of Pulmonary Diseases, Heart Lung

Centre Utrecht, Utrecht, The Netherlands
This Page Intentionally Left Blank
CONTENTS
Introduction Claude Lenfant iii

Preface v
Contributors vii
1. The History of Inhaled Drug Therapy 1

Chris O’Callaghan, Ola Nerbrink, and Mika T. Vidgren
I. Introduction 1
II. Smokes and Vapors 1
III. Inhalation of Droplets 3
IV. The Pressurized Metered-Dose Inhaler 9
V. Asthma Deaths 11
VI. Dry-Powder Inhalers 15
References 18
2. Basic Principles of Particle Behavior in the Human

Respiratory Tract 21
Joachim Heyder and Magnus U. Svartengren
xi
xii Contents
I. Introduction 21
II. Particle Transport onto Airway Surfaces 22
III. Particle Deposition—Definitions and Fundamental
Considerations 25
IV. Total Deposition 27
V. Regional Deposition 33
VI. Modeling of Particle Deposition 37
VII. Consequences for Aerosol Therapy of Particle Behavior
in the Respiratory Tract 38
References 44
3. Structure and Function of the Respiratory System: Developmental

Aspects and Their Relevance to Aerosol Therapy 47
Janet Stocks and Alison A. Hislop
I. Introduction 47
II. Structural Organization of the Respiratory System 48
III. Developmental Changes in Respiratory Function That Will
Influence Aerosol Therapy 71
IV. Conclusions and Future Directions 87
References 89
4. In Vitro Testing of Pharmaceutical Aerosols and Predicting

Lung Deposition from In Vitro Measurements 105
Andy Clark and Lars Borgström
I. Introduction 105
II. Aerosol Characterization Techniques 107
III. In Vivo Characterization Techniques 116
IV. In Vitro Characterization: Issues and Limitations 120
V. Predicting Lung Deposition 126
VI. Summary 138
References 139
5. Factors Affecting the Clinical Outcome of Aerosol

Therapy 143
Eric Derom and Lars Thorsson
I. Introduction 143
II. In Vitro Performance of the Formulation 145
Contents xiii
III. Patient Preference 146

IV. Patient Compliance 147
V. Pharmacodynamic and Pharmacokinetic Properties of the
Inhaled Drug 148
VI. Handling and Maintenance of the Inhaler 152
VII. Relationship Between Pulmonary Deposition and Clinical
Effect 154
VIII. Extrathoracic Deposition, Local Side Effects, and
Systemic Effects 158
IX. Lung Versus Total Bioavailability Ratio (L/T Ratio) 160
X. Studies in Healthy Volunteers 161
XI. Cost-Effectiveness 162
XII. General Conclusions 163
References 164
6. In Vivo Measurements of Lung Dose 173

Mark L. Everard and Myrna B. Dolovich
I. Introduction 173
II. Imaging and Pharmacokinetic Approaches 176
III. Imaging 180
IV. Pharmacokinetic Studies 197
V. Choice of Subjects 200
VI. Relationship Between Drug Delivery and Effect 201
VII. Summary 201
References 202
7. Targeting the Lungs with Therapeutic Aerosols 211

Pieter Zanen and Beth L. Laube
I. Introduction 211
II. Polydisperse Versus Monodisperse Aerosols 212
III. Mechanisms of Desposition 212
IV. Factors That Affect Aerosol Targeting 218
V. Therapeutic Aerosols and Their Targets 222
VI. The Clinical Effects of Targeting 230
VII. Targeting the Lungs During Nose Breathing 251
VIII. Targeting Constricted Airways 253
IX. Targeting Different Age Groups 258
X. Summary 260
References 261
xiv Contents
8. Nebulization: The Device and Clinical Considerations 269

Gerald C. Smaldone and Peter N. LeSouef
I. Nebulizers and the Clinician 269
II. Principles 270
III. Gravimetric Measurements and the
“Standing Cloud” 271
IV. Importance of Breathing Pattern 273
V. The Concept of Inhaled Mass and Lung Deposition 274
VI. Nebulizer Reproducibility 279
VII. Components of the Nebulizer Charge 280
VIII. The Lung Dose 283
IX. Measuring Particle Size During Nebulization 287
X. Labeling Pharmaceutical Nebulizer Solutions for Bench
Testing and Deposition Studies 292
XI. Route of Inhalation 294
XII. Mechanical Ventilation 294
XIII. Summary 300
References 300
9. New Nebulizer Technology 303

John H. Dennis and Ola Nerbrink
I. Introduction 303
II. Background 304
III. New Nebulizer Technology 306
IV. The Ideal Nebulizer 307
V. Examples of New Nebulizer Technologies 309
VI. Assessment of Performance of New Nebulizer Technology 326
VII. Development of Clinical Nebulizer Guidelines Within the
European Respiratory Society 330
VIII. Summary 331
X. Final Note 334
References 334
10. The Metered-Dose Inhaler 337

Chris O’Callaghan and Paul Wright
I. Introduction 337
II. What Is a Pressurized Metered-Dose Inhaler (pMDI)? 338
III. pMDI Technique 341
IV. Airway Deposition and the Effects of Anti-Asthma Drugs
Contents xv
Delivered from MDIs 346

V. Use of pMDIs in the Very Young and in the Elderly 349
VI. Safety of pMDIs 350
VII. Breath-Actuated MDIs 351
VIII. The Synchroner 356
IX. The Spacehaler 356
X. Generic pMDIs—Salbutamol and Steroids 358
XI. CFC-Free MDIs 358
XII. CFC-Free Steroids Delivered by pMDI 361
XIII. Compliance Monitors 363
XIV. Future Research 364
References 365
11. Propellants 371

Martyn R. Partridge and Ashley A. Woodcock
I. Introduction 371
II. The Background 371
III. Government Response 373
IV. New Propellants for pMDIs 376
V. Implementing the Montreal Protocol 381
VI. The Kyoto and the Montreal Protocol 386
VII. MDI Propellants: Where Will We Be in 2015? 387
References 387
12. Spacer Devices 389

Hans Bisgaard, Jacob Anhøj, and Johannes H. Wildhaber
I. Introduction 389
II. The Objectives of a Spacer Device 390
III. When Should a Spacer Be Used? 392
IV. Specifications of Spacer Devices 394
V. Sources of Aerosol Loss Within Spacers 395
VI. Effect of Spacer Construction on Dose Delivery 403
VII. The Optimal Spacer for Young Children 404
VIII. Choice of Spacer Depends on Choice of Drug 405
IX. Use of Spacers 406
X. Use of Facemasks with Spacers 407
XI. Use of Spacers in Neonates and Infants 409
XII. Use of Spacers in Ventilated Patients 409
XIII. Influence of Spacers on Lung Dose 410
xvi Contents
XIV. A Spacer for a Dry-Powder Inhaler 411

XV. Conclusion 412
References 415
13. Dry-Powder Inhalers 421

Lars Borgström, Hans Bisgaard, Chris O’Callaghan,
and Søren Pedersen
I. Introduction 421
II. Dry-Powder Formulations 422
III. Dispersion of Powders in a DPI 425
IV. Aerosol Generation from a DPI 425
V. Particle Size Determination from DPIs 427
VI. Inhalation Resistance of DPIs 428
VII. The Clinical Importance of the Resistance of a DPI 430
VIII. Humidity 434
IX. Dry-Powder Inhalers 435
X. Lung Deposition via DPIs 439
XI. Variability in Lung Deposition 441
XII. Safety of DPIs 442
XIII. Concluding Remarks 442
References 443
14. Compliance with Asthma Medicine 449

Michael E. Hyland and Cynthia S. Rand
I. What Is Compliance? 449
II. Measurement of Noncompliance and Prevalence 453
III. Reasons for Unintentional Noncompliance 456
IV. Reasons for Intentional Noncompliance 459
V. Issues in Pediatric Compliance 466
VI. Diagnosing Noncompliance 467
VII. Targeting Device/Oral Therapy According to Patient
Profile and Individualizing Advice 471
VIII. Summary and Further Research 471
References 472
Author Index 477

Subject Index 505
1
The History of Inhaled Drug Therapy
CHRIS O’CALLAGHAN OLA NERBRINK
University of Leicester AstraZeneca R&D

Leicester, England Lund, Sweden
MIKA T. VIDGREN
University of Kuopio
Kuopio, Finland
I. Introduction
The treatment of respiratory disorders such as bronchial asthma has varied

greatly. Therapies have included hot and cold compresses or baths, concentrated
showers to the back of the head, as well as dried fox lungs, owl blood in wine,
and chicken soup (1). In this chapter we outline the history of inhaled medica-
tions in the treatment of respiratory disease.
II. Smokes and Vapors
Inhalation therapy was first described in Ayurvedic medicine more than 4000
years ago (2). The leaves of the Atropa belladonna plant, containing atropine,
were smoked in diseases of the throat and chest (3). Often a paste consisting of
Datura species was dried and fixed into a pipe. The length of the pipe controlled
the strength of the inhalant. The Hindu physician Charaka advised the use of
spices, gum resins, and fragrant wood that were ground into powder and made
into a paste. The paste was then smeared over thin tubes or sticks and lighted.
The smoke was inhaled to treat diseases of the throat and chest (3). A number of
1
2 O’Callaghan et al.
other ancient cultures recommended inhalation of a variety of substances for

medicinal purposes. The ancient Greeks sent consumptive patients to the pine
forests of Libya (3) to benefit from volatile gases released there. Ancient Egyp-
tians inhaled vapors released when plants of Hyosycamus muticus were placed
on hot bricks (4). Even Hippocrates supported the use of hot vapors for inhala-
tion purposes (5).
More recently, in 1664, Bennet (3) employed inhalation therapy for the
treatment of tuberculosis. In 1810, Laennec (3) used vapors released from a vari-
ety of sources including aromatic plants, balsams, and sulfur for the treatment of
chest infections. In 1802, the Indian use of Datura was introduced into the
United Kingdom (6). It was initially smoked in a pipe alone or in a mixture with
tobacco. At the same time, Datura stramonium was substituted by Datura ferox
for relief of the paroxysms of asthma. Later the Datura-tobacco mixture found
its way to the cigarette (Fig. 1). Best known were Potter’s asthma cigarettes,
which contained shredded D. stramonium leaves (7). Since smoke is by defini-
tion a two-phase system where solid particles are mixed with a gas phase, ciga-
rette smoke can be considered as a colloidal dry-powder aerosol system. The
clinical effects of Potter’s asthma cigarettes were studied by Elliot and Reid (8)
in the randomized crossover study, which illustrated that smoking Potter’s
Figure 1 Asthma cigarettes containing shredded stramonium leaves.

The History of Inhaled Drug Therapy 3
asthma cigarettes caused a bronchodilator effect analogous to that seen with the
inhalation of ipratropium by aerosol.
III. Inhalation of Droplets: The Early Nebulizers
Until the beginning of the nineteenth century, all inhalation therapy had relied on
the use of vapors. In the late 1820s the inhalation of liquid droplets was devel-
oped and the use of nebulizers in inhalational therapy became established
(3,9,10). In 1829, Schneider and Walz (10) constructed the first apparatus that
could break liquid up into droplets. Later, Auphan constructed an “inhalato-
rium,” where liquid in the form of mineral water was thrown against the walls of
a room to form water droplets. In 1860 Sales-Girons presented a portable device
(Fig. 2) constructed by Charrières. From this time an increasing number of de-
vices were described and the inhalation of liquid droplets for inhalation therapy
became more popular. The devices were often referred to as an apparatus for the
“pulverization of liquids.” Almost simultaneously, steam-driven devices such as
the Seeger steam apparatus (11) were developed. Later on, compressed oxygen
was also used to drive the atomization process. In 1872, the term nebulizer was
defined in the Oxford dictionary.
There are many similarities between these early devices and modern nebu-
lizers. Many of the devices had a detached “drug” container. Liquid was sucked
Figure 2 The Sales-Girons portable device from 1860. (From Ref. 12.)
to the atomization point by the negative pressure generated by steam or oxygen,

under pressure, suddenly expanding at the exit nozzle. Baffle systems were not
incorporated into the early nebulizer. Looking back, we would now define such
early devices as atomizers. Today, nebulizers are regarded as atomizers that in-
corporate a baffle system to select out smaller particles for inhalation. This
“modern” type of nebulizer appeared in the early twentieth century.
The inhalation of nebulized aerosols was advertised as beneficial for many
ailments. The Sales-Girons device was advised for pharyngitis, laryngitis, bron-
chitis, pain, catarrh, asthma. tuberculosis, and sleeplessness (12). The liquids and
substances inhaled varied widely and included mineral water containing sulfur,
iodine, and chlorine; sedatives; antiseptics; and belladonna. In 1882, Yeo (3) pre-
scribed the use of a mixture of creosote, carbolic acid, eucalyptus, or turpentine
with equal parts of spirit and chloroform in his oronasal inhaler. The Yeo inhaler,
which is poorly described, is probably more of a vaporizer than an early nebu-
lizer. Earlier, in 1878, Lee (3) performed antiseptic experiments using a jet of
steam containing a mixture of phenol and water. Iodoform, iodine, thymol, and
terebene were also used (3).
Aerosols were advocated for other uses. In 1870, Sir Joseph Lister, profes-
sor of clinical surgery at Kings College, presented a method for the sterilization
of the air during surgery (13). It consisted of a nebulizer apparatus called the Lis-
ter steam spray (Fig. 3). The nebulizer produced a steam containing carbolic acid
by sucking the carbolic acid/water mixture, contained in a separate vessel, to the
atomization point, with the aid of the expanding steam. The method was used to
sterilize the air and to create an atmosphere where the surgical instruments could
be kept without the danger of contamination. According to Pennington (13), the
spray was also used when changing dressings. Less than 10 years after its intro-
duction, it was questioned by von Bruns (14). Criticism of this method grew and
Lister abandoned the technique in 1887. In his paper of 1890 (15), he com-
mented, “I feel ashamed that I should have ever recommended it for the purpose
of destroying the microbes of the air.”
The question of whether aerosols, or “pulverised liquids,” reached the
lungs was debated intensively; that they did was not widely accepted until
1862, when Poggiale presented his report to the Paris Medical Academy (16).
This triggered further investigations into the inhalation and deposition of
aerosolized liquids in the airways. In 1872, Waldenbourg (17) conducted and
presented several studies on the bronchial deposition of pulverized liquids. He
concluded that approximately 25% of the dose was deposited in the mouth and
larynx and approximately 30% passed beyond the larynx. Accordingly, he rec-
ognized that bronchial deposition depended on the physical characteristics of
the patient, such as the position of the tongue in the mouth and the inspiratory
volume, in addition to the patient’s pathological conditions. As a conclusion,
he even recommended gargling after the treatment. Heubner’s (18) experi-
Figure 3 The Lister steam spray of 1870. (From Ref. 59.)
ments, reported in 1923, helped to convince others that aerosolized liquids

reached the lungs.
Multiple large nebulizers with substantial output capabilities were used to-
gether as a collective inhalation chamber in the coal mines in South Africa and
Germany in the 1930s (18). The nebulizer used was an 8- or 16-nozzle device
placed in a cabinet in a corridor (Fig. 4). The corridor could be several hundred
meters long and could contain a number of nebulizer cabinets (Fig. 5). The nebu-
lizer was filled with what was considered to be a mucolytic and bronchodilating
solution. At the end of the miners’ shift, nebulization was commenced, and the
miners walked slowly through the mist-containing corridor, inhaling the aerosol.
A further example of collective inhalation was found in Germany (J. Heyder,
personal communication). A large aerosol generator was located in a hallway of
about 100 m long with piles of branches at the side. Salt solutions were allowed
to drip onto the branches. Each time a falling drop struck a branch, smaller
droplets were generated. Patients walked in the hallway inhaling the particles.
This was considered a simple and efficient way to produce large volumes of ther-
apeutic aerosols for inhalation.
The development and use of adrenaline in the treatment of asthma was a
major advance. In 1900, Solis-Cohen (19) injected crude adrenal extract into pa-
tients with asthma and hay fever. Shortly afterwards, Bullowa and Kaplan (20)
reported the successful use of adrenaline injection. This became established as a
standard therapy for relief of severe attacks of asthma. By 1911 a nasal spray
containing adrenaline was in use for asthma and as a decongestant for hay fever
and rhinitis.
Figure 4 Collective inhalation device used in Germany and South Africa (1930). A 16-
nozzle nebulizer is fitted in a wall-mounted cabinet. (From Ref. 18.)
Figure 5 Collective inhalation device; the exposure corridor. (From Ref. 18.)
In 1911, Zeulzer (21) described the use of Glycerinan, a mixture of Epire-

nan, an adrenaline analogue, in water and glycerine. It was given via a Draeger
nebulizer (constructed by Professor Spiess) to patients with chronic bronchitis,
chronic laryngitis, croup-related pneumonia, interstitial pneumonia, and tubercu-
losis. The nebulizer used compressed air or compressed oxygen and was oper-
ated at 5 or 12 L/min. The first report of adrenaline being administered by an
inhaler in the United Kingdom came from Guy’s Hospital when it was used in
the nebulized form in 1929 (22).
The Draeger or Hirth apparatus (22) and also a nebulizer called Apneu (23)
became popular. Bulb nebulizers, where the patient operated the device by press-
ing a rubber bulb connected to the nebulizer to generate the gas flow, became
popular (23). These nebulizers generated an aerosol with a wide droplet-size dis-
tribution and a large fraction of nonrespirable droplets. In the 1930s, glass-bulb
nebulizers such as the DeVilbiss No. 40 and equivalent (Fig. 6) and the
Vaponephrine nebulizers (Fig. 7) were popular. The Vaponephrine nebulizer was
one of the first with a baffle close to the generation point. Not surprisingly, sub-
sequent investigations showed that the DeVilbiss device produced larger
droplets than the Vaponephrine device (24).
In 1946, electrical pumps providing a continuous flow of air were advo-
cated. The Collison nebulizer (25), made of ebonite with a plate baffle to fil-
Figure 6 The Dyspne-Inhal. Laboratoire Du Dyspne-Inhal, Clermont-Ferrand, France,

a copy of the DeVilbiss 40 nebulizer. (Courtesy of Kurt Nikander, AstraZeneca.)
Figure 7 The Vaponephrine device with baffle (B). This was a blown-glass construction.
ter out large drug particles, became the most popular nebulizer in the United
Kingdom. The Collison had one serious defect: the liquid was fed into the spray
through three blind holes in an ebonite spray unit. Since most liquids used in
nebulizers tended to form a deposit, these holes invariably became blocked and
were difficult to clean. The glass spray-type of nebulizer had two serious defects.
First, the sprays varied a good deal in their efficacy because they were “hand
made.” Second, the feed pipe of the spray was liable to become blocked after a
period of use and attempts to clear it were often associated with breakage. In
1958, Wright (26), working in the pneumoconiosis research unit of the Medical
Research Council, designed a nebulizer bearing his name, which was robust and
easy to clean. It was entirely made of Perspex. In addition to being practically
unbreakable and easy to clean, one of the criteria used as an indicator of good
performance, was the ability of the nebulizer to produce droplets ranging in size
between 1 and 6 µm in diameter at a given gas flow.
In 1945, the introduction of penicillin was followed swiftly by attempts to
nebulize it directly to the lungs. A device know as the Deedon inhaler (Moore
Medicinal Products Ltd., Aberdeen, Scotland) was a neat, hand-held inhaler
made entirely from plastic and intended for the administration of penicillin or
antispasmodics. It was suggested that the fine mist of penicillin was likely to
penetrate as far as the small bronchi and bronchioles. Penicillin, in 30% glycer-
ine, placed in the reservoir was administered in 6 to 7 min by squeezing the rub-
ber bulb at each inspiration. The makers also advertised an electric pump, at a
cost of £20, which was considered expensive by the Lancet (27). Other com-
pounds, such as streptomycin, were also nebulized.
The next major advance in inhalational therapy for asthma was the intro-
duction in 1951 of isoprenaline. In 1940, Konzett of Boehringer Ingelheim found
that an analogue of adrenaline, its N-isopropyl derivative (28), helped to relieve
the bronchospasm of asthma when inhaled. Knowledge of its development be-
came available when the U.S. State Department investigated work carried out by
German chemical manufacturers during the war. The drug, named isoprenaline,
produced the bronchodilating effect of adrenaline, but was relatively free from
troublesome pressor activity (29). The compound was introduced into clinical
use in 1951.
The first ultrasonic nebulizer was introduced in the 1960s (11). It operated
by vibrating a piezoelectric crystal inducing high-frequency waves, which
caused droplets to break free from the surface of a liquid. Further developments
of the nebulizer are dealt with in later chapters.
IV. The Pressurized Metered-Dose Inhaler
The most important development in antiasthma drug delivery was the advent of
the metered-dose inhaler in 1956, which resulted in a huge increase in the use of
antiasthma therapy. Sales of pressurized metered-dose inhalers now run at ap-
proximately 500 million per year. However, the introduction of this device was
not without problems. This section of the chapter covers the early use of propel-
lants in atomization, the origin of the metered-dose inhaler, and the epidemic of
asthma deaths.
The power of propellants to atomize liquids was realized in the late nine-
teenth century. Helbing and Pertsch (30), from Lyon, France, described a patent
for improving the preparation and application of coatings and insulating materials
for medical purposes. Methyl and ethyl chlorides were mixed with certain
“gummy or fatty materials.” The heat of the hands surrounding the vessel in
which the mixture was contained immediately caused the ethyl or methyl chloride
inside the vessel to evaporate. Evaporation increased the internal pressure and
the solution was ejected through the orifice in a fine jet or spray. On the surface of
the target, the methyl or ethyl chloride in the ejected solution evaporated rapidly,
leaving the residue as a uniform coat, layer, or varnish. Helbing and Pertsch felt
that their invention would be particularly useful in forming a protective coating to
a wound. At the turn of the century, Gebauer (31) found that partial vaporization
of a propellant liquid prior to final atomization at the spray nozzle produced a
finer spray; he went on to describe the first use of a twin-orifice expansion cham-
ber. The discovery of freon propellants—such as 11, 12, 22, and 114 in the 1930s
and 1940s—made liquefied gas generators a realistic option. The first commercial
systems using propellants, introduced during the 1940s, were nonmetered devices
designed for spraying insecticides.
The pressurized metered-dose inhaler (pMDI) for the delivery of anti-
asthma drugs originated in the U.S. cosmetic industry. George Maison, the presi-
dent of Riker Laboratories, and Irvin Porush, who worked in Riker’s
pharmaceutical development laboratory, are credited with the development of
the first pMDI (32). Experiments were conducted to formulate pressurized
aerosols of isoproterenol and epinephrine, which had been dissolved in alcohol,
using the freon propellants 12 and 114.
In 1954, Philip Meshburg invented and patented a metering valve, in-
tended for use by the perfumery industry, which allowed approximately 50 µL to
be dispensed (33). The Meshberg valves were attached to plastic-coated glass
vials that were used elsewhere as containers for the delivery of perfume aerosols.
This initial MDI was connected to a 3-in. plastic mouthpiece, probably to de-
crease the impact of the inhaler’s 50% ethyl alcohol solution on the oropharynx
(Fig. 8). This mouthpiece was the forerunner of the modern extension tubes that
are used to decrease the oropharyngeal deposition of drug. Initial clinical trials
were carried out by Dr. Karr of the Veterans’ Administration Hospital in Long
Beach, California, in 1955 (32). The first published clinical trial showing suc-
cessful treatment was by Friedman in 1956 (34). In March 1956, the Medihaler-
Iso and Medihaler Epi were approved and launched.
At this very early stage, the possibility of using the lung to deliver sys-
temic medication was considered possible. Other drug formulations intended for
use in an MDI were also patented. These included both nicotine and insulin. Al-
though insulin was shown in animal experiments to cause hypoglycemia, the ef-
fect was very variable and this initiative was not then pursued. It is of interest
Figure 8 The original metered-dose inhaler with its 3-in. plastic mouthpiece. It was made
of glass with a Meshburg metering valve attached. (Courtesy of 3M Pharmaceuticals.)
that inhaled insulin is now in phase 3 trials and may become a standard therapy
for diabetic patients.
The next major development was by Dr. Charlie Thiel, a chemist at Riker
(35). He used a surfactant, sorbitan trioleate (span 85), as a dispersing agent
mixed with a suspension of micronized drug and propellant. The suspension
aerosols appeared to deliver a respirable drug considerably more efficiently than
the early alcohol solution formulations and allowed poorly soluble drugs to be
aerosolized. In 1957, bronchodilator products were switched to suspensions.
This switch resulted in many complaints because—although the suspensions ap-
peared more effective—patients missed the taste of the alcohol, which they asso-
ciated with a subsequent feeling of well-being!
Over the next years, the MDI was altered in a number of ways to im-
prove the reproducibility of its output. It was noted very early on that if it
stood upright for any length of time, it did not release a dose when fired for
the first time. Significant drug was delivered only on the second shot. There-
fore, a cup was introduced within the MDI, surrounding the valve, with an en-
trance at the top, so that the liquid formulation would not drain out when the
valve sat upright. This markedly reduced loss of prime, although as we know
that loss of prime with standing still occurs, as described in detail by Cyr and
colleagues (36).
V. Asthma Deaths
The popularity of the MDI grew with advertisements for its use, which first ap-
peared in the British Medical Journal in the early 1960s (Fig. 9). During the
1960s, in the United Kingdom and in a number of other countries, there was a
sudden rise in the mortality of patients with asthma. From 1961, there was a
steady and progressive rise in asthma mortality, which was most marked among
patients aged 5 to 34. Reports of three deaths in which excessive use of a pMDI
was considered to be a contributory factor were published in Australia in 1964,
and a warning from the Autralian Minister of Health was given (37). In August
1965, Greenberg (38), a thoracic physician from Cambridge, sent a letter to the
Lancet in which he recorded eight deaths associated with the use of the new
MDI. In 1967, Greenberg and Pine (39) stated in the British Medical Journal
their suspicion that patients with asthma were killing themselves with excessive
use of MDIs. Richard Doll and Frank Spizer from Oxford and Peter Heaf and
Leonard Strang from London (40) reported that there had been a 42% increase in
the overall death rate between 1959 and 1964. The most seriously affected group
were children between the ages of 5 and 14 years.
In June 1967, the Committee of Safety in Medicines (41) issued a warning
about the need for care in prescribing and using aerosols, emphasizing their great
Figure 9 An early advertisment for pressurized metered dose inhalers appearing in the
British Medical Journal in the early 1960s. (Courtesy of the British Medical Journal.)
value in treatment, but advising patients or parents to call their doctors if they
failed to achieve the relief they usually experienced. From 1968 on, MDIs of an-
tiasthma medications could be obtained in the United Kingdom only by prescrip-
tion, having been available over the counter prior to this. In 1969, Bill Inman and
Abe Edelstein (42), from the Committee on the Safety of Drugs, published a pa-
per in the Lancet entitled “The Rise and Fall of Asthma Mortality in England and
Wales in Relation to the Use of Pressurised Aerosols.” In this paper, the true ex-
tent of the scale of asthma mortality was revealed.
When the changes in death rate were compared with estimates of prescrip-
tions, it could be seen that the rise and fall in the death rates had followed the
graph of sales of pressurized aerosols almost exactly (Fig. 10). In children 4 years
of age and below, there had been no change in death rates. These patients had not
been prescribed aerosols because they were not old enough to use them appropri-
ately. Between the ages of 15 and 34, it was calculated that there had been more
than 960 deaths, and in those over age 35, approximately 2300 in excess of those
expected. Inman and Adelstein (42) proposed the subsequent fall in mortality
might have been brought about either by a reduction in the number of patients
using aerosols or by a reduction in the amount used. It was suggested that both
700
600 Total sales

Sales &
prescriptions
500
( 1000)
400
300
Prescriptions
200
100
Direct sales
0
40
Deaths 30
20
10
0
1959 '60 '61 '62 '63 '64 '65 '66 '67 '68
Figure 10 The rise and fall in death rates during the epidemic of asthma deaths was
mirrored by the rise in sales of pressurized metered-dose aerosol inhalers. (From
Ref. 42.)
doctors and patients may have been lulled into a false sense of security by effec-
tive bronchodilators. When medication failed to produce the expected relief, the
patients may have continued to use the aerosol and thus to overdose. The doctor
may have failed to recognize the resistance to treatment while the patient contin-
ued to deteriorate. The reason for the fall in the death rate may have been the
greater understanding of the serious nature of an asthma attack and earlier ad-
mission to hospital with more effective treatment. It has been suggested that
many lives would have been saved if steroids were started, or the dose already
employed increased, whenever asthma deteriorated (43). Evidence that asthmat-
ics actually overdosed themselves is circumstantial and is mainly derived from
the accounts of those who witnessed the patients’ excessive use of aerosols or
who found such patients lying dead and clutching empty or partially empty can-
isters. Concentrations of isoprenaline or orciprenaline present in the body after
death were not determined in these cases, and there were no characteristic post-
mortem changes attributable to the overdose.
However, the main toxicity of excess usage of an MDI was thought to be
related to the fluorocarbon propellants. At a similar time as the asthma deaths
were being investigated, there were reports from the United States that sudden
deaths had occurred among individuals who were abusing aerosol propellants by
filling plastic bags with them and then inhaling their contents (44). The mecha-
nism of death was assumed to be cardiac arrhythmias, because autopsy failed to
reveal any other cause. In the United Kingdom, the mechanism of death among
asthmatics has never been clearly established.
It was shown that conscious dogs breathing moderate concentrations of
fluorocarbon for 5 min would develop severe ventricular arrhythmia when chal-
lenged with intravenous bolus doses of adrenaline (45, 46). Dollery and col-
leagues (47), from the Hammersmith hospital, studied the toxicity of propellant
gases in humans. The eight patients who volunteered for the study had severe
asthma and took either one or two inhalations from their inhalers at intervals of
30 or 60 s. The arterial peak concentration of fluorocarbon occurred 10–20 s af-
ter the last inhalation. The fall in the concentration in arterial blood was rapid
and declined to half in 18–38 s with fluorocarbon 11 and 12–24 s with fluorocar-
bon 12. The predicted peak myocardial levels were 10% or less than the pre-
dicted myocardial concentrations that sensitized the myocardium of dogs studied
by Clark and Tinsten (46). To test extreme conditions, one volunteer took an in-
halation from a pressurized aerosol placebo dispenser on every breath for 30, 60,
and 120 s, breathing at a rate of 12 breaths per minute. The predicted peak my-
ocardial concentration considerably exceeded the value that would sensitize the
dog heart to circulating or injected adrenaline (48).
The results suggested that there should be a factor of safety of about 10
when the inhaler is used in the manner recommended by the manufacturers. As
long as several normal breaths are taken before the inhaler is used again, the
alveolar and thus the arterial and myocardial concentrations fall rapidly. Dollery
(47) concluded that there was unlikely to be a hazard from the propellants if the
inhaler was used as recommended, but there could be a hazard in conditions of
excessive overdose. There are some concerns with regard to this interpretation,
as in one of the dog experiments, one of the dogs tested was very much more
sensitive than the others. In addition, we now know that in patients with severe
asthma, the actual deposition of drug within the respiratory tract may vary
greatly between patients. The effect of these factors and the use of isoprenaline,
a nonselective beta2 agonist, in patients during acute attacks of asthma (when
they are likely to be hypoxic) can only be guessed.
The lesson that must not be forgotten is that any new treatment must be in-
troduced gradually and under close supervision. The importance of pharma-
covigilance and reporting cases of possible toxicity cannot be overemphasized.
VI. Dry-Powder Inhalers
The first inhalation system delivering solid drug particles was introduced in the
late 1800s. This system, called the carbolic smoke ball, was patented by Freder-
ick Augustus Roe in England in 1889 as a device to facilitate the distribution, in-
halation, and application of medicated powders (49). The device consisted of a
rubber ball containing fine powder charged with carbolic acid (phenol) (Fig. 11).
Remedies such as glycyrrhiza and white hellebore (Veratrum veride) were com-
monly packed into the ball. The drug dose was released in puffs and inhaled via
the mouth or nostrils. The carbolic smoke ball became a popular asthma and hay
fever remedy (50). The product was marketed by offering a reward of £100 ster-
ling to anyone contracting influenza after using the product three times daily for
2 weeks (Fig. 12). This resulted in several claims against the company (49) and
the withdrawal of the offer.
Adrenocorticotropic hormone (ACTH) and cortisone became available in
the 1940s (51). In 1949 Bordley and colleagues (52) reported the beneficial ef-
fect of intramuscular ACTH given to five asthmatic patients. Reeder and Mackey
(53) reported that nebulized cortisone delivered directly to the lungs by inhala-
tion in a patient with bacterial pneumonia caused remission of symptoms. Fol-
lowing this report, Gelfand (54) gave nebulized cortisone to five asthmatic
patients. The drug was delivered via a DeVilbiss nebulizer on an hourly basis be-
tween 9 A.M. and 10 P.M. A total of 50 mg per day was given. In four of the five
patients, a favorable response was observed. By the end of the seventh day, al-
most all signs of bronchospasm had disappeared. Relapses were observed in
three of the four successfully treated cases 4 to 5 days after treatment had
stopped. In 1955, Foulds (55), a registrar in ophthalmic surgery, and colleagues
delivered hydrocortisone powder to 15 patients with bronchial asthma. The parti-
cle size of hydrocortisone powder was said to be less than 5 µm. Although the
powder inhaler was not described, an estimated 7.5–15 mg was inhaled per day.
After using hydrocortisone powder for 2 to 3 weeks, patients were given car-
tridges containing an inert powder for the same period. After this, some of them
were changed back to hydrocortisone. In 11 patients, the treatment caused a def-
inite improvement of the asthma with the number of isoprenoline inhalations
dropping to half or less. When inert powder was substituted, the improvement
persisted for up to 3 weeks. When the asthma had returned to its former severity,
resumption of hydrocortisone again brought about relief. In contrast to these
studies, a nebulized solution of hydrocortisone was found to be ineffective when
trialed by Brockbank and colleagues in 1956 (56).
Although a number of patents for powder delivery devices for medicinal
purposes were filed from the middle of the twentieth century, the first widely
used powder inhaled was sodium cromoglycate.
In the mid-1950s, Khellin analogues were being investigated as potential
Figure 11 The India rubber carbolic smoke ball.
bronchodilators. Active compounds were examined in sensitized guinea pigs ex-

posed to aerosols of egg white in order to induce a laboratory model of an
asthma attack. Roger Altounyan, a physician who had severe asthma, tested
compounds thought to have antiasthma properties on himself by inhaling a
preparation of guinea pig hair, which he knew would induce an asthmatic attack.
By 1958, he had found that several analogues of Khellin were protective. One in
particular had no bronchodilating activity and afforded animals no protection
against histamine; however, it protected Altounyan from the effects of guinea pig
hair. The medication was effective only if inhaled, but as inhalation was found to
Figure 12 Advertising for the carbolic smoke ball. A reward of £100 was offered to
those who genuinely caught influenza following use of the carbolic smoke ball.
irritate the lungs, the project was abandoned. However, in 1963, it was found that
one of the compounds was contaminated with a highly active material. A series of
bischromones were subsequently prepared for Altounyan to inhale. In 1965, he re-
ported that sodium cromoglycate (57) was an ideal protective drug when inhaled.
Altounyan and Howell, a company engineer, developed a special device that en-
abled the drug to be inhaled as a dry powder liberated from a pierced capsule. The
results of the first clinical trial (58) were reported in 1967. Sodium cromoglycate,
delivered in powder form from the Spinhaler, was marketed with great success.
The worldwide market for inhaled drug delivery is now approaching £5 bil-
lion each year. The drug delivery devices now used are described in detail in the re-
mainder of this book. It will become obvious to the reader that while improvements
have been made in aerosol drug delivery, further developments are still needed.
Acknowledgment
The 20th Century History of Medicine Department, The Wellcome Trust.
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2
Basic Principles of Particle Behavior
in the Human Respiratory Tract
JOACHIM HEYDER MAGNUS U. SVARTENGREN
GSF–National Research Center for Karolinska Institutet

Environment and Health Stockholm, Sweden
Munich, Germany
I. Introduction
If inspired particles were carried only convectively with the bulk of airflow,
losses of these particles in the respiratory tract would be negligible. However, all
inspired particles experience a nonzero chance of being lost. This is due to parti-
cle transport toward airway and airspace surfaces as a result of mechanical and
electrical forces acting upon the particles. Upon contact with these surfaces, the
particles are deposited. The human respiratory tract can therefore be considered
as an “aerosol filter,” removing particles from the inspired air. The effectiveness
of this filter depends on
The physicochemical properties of the inspired particles
The breathing pattern and morphology of the subject inspiring the particles
The mode of breathing (nasal or oral)
The distribution of particles in the inspired air
The following pages discuss how the “filter characteristics” of the human
respiratory tract or its regions are affected by these factors and what implications
this has for an efficient aerosol therapy. This chapter also summarizes the devel-
opment of the field over the last two decades:
21
22 Heyder and Svartengren
Experimental determination of particle deposition in the human respiratory

tract under laboratory conditions (summarized in Ref. 1).
Development of a semiempirical deposition model based on these experi-
mental laboratory data (2).
Adaptation of the model to all available experimental deposition data and
extension of the model to ultrafine particles by the International Com-
mission on Radiological Protection (ICRP) (3).
Current applications of the ICRP model for predicting deposition of phar-
maceutical particles.
Since pharmaceutical particles often look like spheres and these particles
are usually administered per os, the behavior in the respiratory tract of orally in-
spired spherical particles is the focus of attention in this chapter.
II. Particle Transport onto Airway Surfaces
Because of the mechanical and electrical forces acting upon inspired particles,
particle trajectories are different from airstream lines, so that particles are trans-
ported toward surfaces of the respiratory tract. However, whereas all inspired
particles are exposed to mechanical forces, only charged particles are exposed to
electrical forces. Since pharmaceutical particles are usually not heavily charged,
particle transport in the human respiratory tract is governed by mechanical trans-
port: diffusional, gravitational, and inertial (Fig.1). Since diffusional and gravita-
tional transport are time-dependent transport phenomena, particles are
simultaneously transported by both mechanisms. However, when particles cover
more than about 30 µm s-1 by diffusional transport, the contribution of gravita-
tional transport becomes negligible. When they cover more than about 30 µm s-1
Diffusional transport
Inertial transport x
Gravitational transport
Figure 1 Illustration of particle transport onto airway surfaces.

Particle Behavior in the Respiratory Tract 23
by gravitational transport, the contribution of diffusional transport becomes neg-

ligible. On the other hand, inertial transport is a velocity-dependent transport
phenomenon. It becomes effective for particle deposition only when particles
cover more than 30 µm s-1 by this transport phenomenon.
A. Diffusional Particle Transport (Diffusion)
Aerosol particles of dimensions comparable with the mean free path of gas mol-
ecules (about 0.06 µm) recognize their gaseous surroundings as composed of in-
dividual molecules, and every collision of a particle with a gas molecule changes
its kinetic energy and direction of motion; as a result, the particle moves at ran-
dom through the gas (Brownian motion or diffusion). The random displacement
a particle covers by this transport increases with time and with decreasing parti-
cle diameter. It is independent of the particle density.
In the respiratory tract, only ultrafine particles (particles smaller than 0.1
µm in diameter) are deposited solely due to diffusion, since those particles
cover more than 30 µm s-1 by diffusional transport (Fig. 2). For all ultrafine
particles of the same size, deposition is the same regardless of their density.
Because of the time-dependence of diffusional particle transport, it is antici-
pated that diffusional deposition of ultrafine particles occurs mainly in lung re-
gions of maximum residence time of the tidal air—i.e., in small airways and in
the lung periphery.
B. Gravitational Particle Transport (Sedimentation)
Particles larger than 0.1 µm are less and less transported by diffusion but settle
more and more under the action of gravity. The displacement of a particle by
gravitational transport increases with time and with particle diameter and den-
sity. In the respiratory tract, spheres of 3 g cm–3 density larger than 0.5 µm, unit
density spheres larger than 1 µm, and spheres of 0.1 g cm–3 density larger than 3
µm in diameter are no longer deposited due to diffusion but solely due to sedi-
mentation, since those particles settle more than 30 µm s–1 (Fig. 2). Because of
the time-dependence of gravitational particle transport, it is anticipated that
gravitational deposition of particles occurs mainly in lung regions of maximum
residence time of the tidal air—i.e., in small airways and in the lung periphery.
C. Inertial Particle Transport (Impaction)
In the branching network of airways, the inspired air is changing its velocity and
direction of motion all the time while it is penetrating into the lungs. Particles car-
ried with the air are therefore exposed to inertial forces all the time. For particles
of sufficient mass, these forces result in an inertial displacement and thus in a par-
ticle transport toward airway surfaces. This displacement increases with particle
1000
ρ = 0.1 g cm
-3
100
10
1
Mean displacement (µm s-1)
10000
ρ = 1 g cm
-3
1000
100
10
1
10000
ρ = 3 g cm-3
1000
100
10
1
0.01 0.1 1 10
Particle diameter (µm)
Figure 2 Mean displacement per second of particles of 0.1, 1 and 3 g cm3 density un-
dergoing diffusional, gravitational, and inertial transport (solid line: diffusional transport;
dashed line: gravitational transport; dotted line: inertial transport).
velocity, diameter, and density. In the respiratory tract, inertial transport con-
tributes to particle deposition for spheres of 3 g cm–3 density larger than 1 µm,
unit density spheres larger than 2 µm, and spheres of 0.1 g cm–3 density larger
than 6 µm in diameter, since these particles cover more than 30 µm s–1 by inertial
transport (Fig. 2). Because of the velocity-dependence of inertial particle trans-
port, it is anticipated that inertial deposition of particles in the respiratory tract oc-
curs mainly in regions of maximum airflow velocity—i.e., in large airways.
D. Summary
In summary, particle transport onto airway surfaces depends on four parameters:

particle diameter, particle density, particle velocity, and the time available for
transport onto airway surfaces. Usually breathing cycle period and respiratory
flow rate are used as substitutes for time and velocity; the dependence of the
mean diffusional, gravitational, and inertial particle displacement on these four
parameters can be summarized as follows:
Particle Particle Breathing

size density cycle period Flow rate
Diffusional displacement Decreases Independent Increases Independent
with size of density with time of flow rate
Gravitational displacement Increases Increases Increases Independent
with size with density with time of flow rate
Inertial displacement Increases Increases Independent Increases with
with size with density of time flow rate
III. Particle Deposition—Definitions and Fundamental

Considerations
Deposition of ultrafine particles is due solely to diffusional transport. Deposition

of larger particles is due to gravitational and/or inertial transport. It is therefore
anticipated that the efficiency of the human respiratory tract to collect inspired
particles decreases with particle size as long as deposition is governed by diffu-
sion and increases with particle size when deposition is governed by sedimenta-
tion and/or impaction (Fig. 3). Deposition assumes a minimum when deposition
due to diffusional transport is equal to that due to gravitational transport. For
particles of 3 g cm-3 density, the lowest deposition is observed for 0.26-µm
spheres; for unit-density particles, it occurs for 0.36-µm spheres. The shape of
the fundamental filter characteristic of the respiratory tract schematically shown
in Fig. 3 is typical for oral breathing of aerosols. The actual shape, however, is
determined by particle density, breathing pattern, and gas volume in the lungs. It
must therefore be emphasized that any statement about the filter characteristics
of the respiratory tract is incomplete without mention of particle density, breath-
ing pattern, and gas volume in the lungs for which it was obtained.
More time is available for transport toward airway surfaces for a particle
inspired at the onset of a breath than for a particle inspired at the end of the
breath. Therefore, even when indentical particles are inspired with the tidal air,
the chance of being deposited will be different for each particle; thus the follow-
ing definition is generally accepted:
Definition: The fraction of inspired particles deposited in the respiratory tract, DF,
is the mean probability that a particle inspired with the tidal air during steady-state
breathing from functional residual capacity is deposited in the respiratory tract. DF
is called total deposition throughout this chapter.
1.0
Diffusion Diffusion Sedimentation
sedimentation impaction
Total deposition
0.5
0
Particle diameter
Figure 3 Schematic filter characteristic of the human respiratory tract for aerosol
particles. Three domains can be recognized; the domain of deposition decreasing with
particle size is solely due to diffusional particle transport, the domain of minimum de-
position is due to simultaneous diffusional and gravitational particle transport, and the
domain of deposition increasing with particle size due to gravitational and inertial par-
ticle transport.
Consequently, DF = 0.5 means that half the particles inspired per breath are de-
posited anywhere in the respiratory tract. Nevertheless, it is possible that all par-
ticles inspired at the onset of a breath are deposited but none of the particles
inspired at the end of the breath.
The same considerations apply for particle deposition in regions of the res-
piratory tract:
Definition: The fraction of inspired particles deposited in region X of the respira-

tory tract, DFx, is the mean probability that a particle inspired with the tidal air dur-
ing steady-state breathing from functional residual capacity is deposited in region
X. DFx are called regional depositions throughout this chapter.
Since each particle inspired with the tidal air can be deposited in only one re-
gion, the sum of all regional depositions equals total deposition.
As far as the behavior of aerosol particles is concerned, the respiratory
tract can be partitioned into four regions:
Extrathoracic region: airways in head and neck

Upper bronchial region: trachea and bronchi (large ciliated thoracic
airways)
Lower bronchial region: bronchioles (small ciliated thoracic airways)
Alveolar region: nonciliated thoracic airways and airspaces
Consequently, total deposition, DF, is the sum of extrathoracic deposition, DFE,

upper bronchial deposition, DFUB, lower bronchial deposition, DFLB, and alveo-
lar deposition, DFA:
DF = DFE + DFUB + DFLB + DFA
IV. Total Deposition

A. Experimental Methodology
According to the definition, total deposition is simply given by
DF = 1 – (number of expired particles / number of inspired particles)
It must therefore be determined during steady-state breathing of well-defined

monodisperse aerosols by counting the number of inspired and expired particles
per breath. Since aerosol photometry is usually applied for monitoring particle
number concentration, c, in inspired and expired tidal air and combined with
pneumotachography for monitoring flow rate, Q, during breathing of the aerosol
(Fig. 4), total deposition can be calculated by
DF = 1 – (∫ c |Q| dt / ∫ c |Q| dt)

te ti
where ti (te) is the time available for inspiration (expiration) of the tidal air.
Inspiration channel
(Air) Photodetector
Inspiration channel
(Aerosol) Flow-
meter
Expiration channel
Mouthpiece
Laser beam
Figure 4 Scheme of the respiratory aerosol probe for determining total deposition of
aerosol particles in the human respiratory tract.
Total deposition can also be determined by measuring the mean particle

number concentration in samples taken from inspired and expired aerosols over
periods of several breaths and taking into account particle losses due to the sam-
pling procedure.
However, regardless of the technique used, the particle number concentra-
tion of the inspired aerosol must remain constant during the entire inspiration. In
case the particle number concentration increases during inspiration, deposition
will be different from that obtained for the case of a decreasing inspiratory parti-
cle number concentration. It must therefore be recognized that it is necessary to
use only aerosols of uniform particle number concentration for the experimental
determination of total deposition.
B. Effect of Particle Dynamics
The dependence of total deposition on particle dynamics is demonstrated in this

chapter for monodisperse spherical particles of 0.9 and 3.2 g cm–3 density and di-
ameters between 0.2 and 10 µm orally inspired with the tidal air from functional
residual capacity by three subjects at patterns illustrated in Fig. 5 (1).
750
250
-250
flow rate (cm3 s-1)
-750
750
250
-250
-750
0 2 4 6 8 10 12 14 16
time (s)
Figure 5 Breathing patterns used for studying total and regional particle deposition
(lines: 4- and 8-s breathing-cycle periods and 750 cm3 s–1 flow rate; dashed lines: 4- and
8-s breathing-cycle periods and 250 cm3 s–1 flow rate).
For all particle sizes deposition increases with time (Fig. 6, top). At a flow
rate of 250 cm3 s-1 deposition is governed by sedimentation but at 750 cm3 s-1
flow rate by impaction. Therefore, the time-dependency of deposition is less pro-
nounced when the aerosols are respired at the high flow rate. When these data are
plotted to illustrate the influence of flow rate on deposition (Fig. 6, bottom) it be-
comes obvious that inertial transport is not effective for deposition anywhere in
the respiratory tract of orally inspired particles smaller than 2 µm in diameter.
In Fig. 7, top the effect of particle density on total deposition is demon-
strated, and it can be seen that 2 µm particles of 3.2 g cm–3 density are deposited
with the same efficiency than 4 µm particles of 0.9 g cm–3 density. This ambigu-
ity can be eliminated by considering the aerodynamic size of the particles.
1.0
0.8
0.6
0.4
0.2
Total deposition
250 cm3s-1 750 cm3s-1

0.0
1.0
750 cm3s-1
0.8 750 cm3s-1
250 cm3s-1 250 cm3s-1

0.6
0.4
0.2
0.0
0 2 4 6 8 10 0 2 4 6 8 10
Figure 6 Oral tidal breathing of 0.9 g cm-3 density spheres with 4- and 8-s breath-
ing-cycle periods and flow rates of 250 and 750 cm3 s-1 from functional residual capac-
ity (lines: 4-s breathing cycle period, dashed lines: 8-s breathing-cycle period): upper
graphs: effect of time on total deposition; lower graphs: effect of flow rate on total de-
position.
1.0
3.2 g cm-3 3.2 g cm-3
0.9 g cm-3
0.8
Total deposition
0.9 g cm-3
0.6
0.4
0.2
250 cm3 s-1 750 cm3 s-1
0.0
0 2 4 6 8 10 0 2 4 6 8 10
1.0
0.9 g cm-3 0.9 g cm-3
3.2 g cm-3 3.2 g cm-3
0.8
Total deposition
0.6
0.4
0.2
250 cm3 s-1 750 cm3 s-1
0.0
1 3 5 7 9 1 3 5 7 9
Aerodynamic particle diameter (µm)
Figure 7 Oral tidal breathing of spheres of 0.9 and 3.2 g cm-3 density with 8-s breath-
ing-cycle period and flow rates of 250 and 750 cm3 s-1 from functional residual capacity:
upper graphs: effect of particle density on total deposition; lower graphs: verification of
the aerodynamic particle diameter concept for the human respiratory tract.
C. Concept of Aerodynamic Particle Diameter

Definition: The aerodynamic diameter of a particle is the diameter of a fictitious
sphere of unit density which, under the action of gravity, settles with the same ve-
locity as the particle in question.
From Fig. 7 (top) it is obvious that the transport properties of a small heavy
sphere can be identical with that of a large light sphere. When both spheres are
transported with the same velocity, they exhibit the same aerodynamic behavior
and thus the same deposition. This velocity is determined by the geometrical size
and the density of the particles. All particles of diameter, d, and density, ρ, behave
aerodynamically in the same way as long as the value of the product (ρd2) is the
same. In this case, all these particles experience identical gravitational displace-
ment. Since both gravitational and inertial transport are dependent on (ρd2) they
also experience identical inertial displacement.
In reality it is not entirely true, that particles characterized by identical
(ρd2) experience identical displacement due to the action of mechanical forces.
The displacement is influenced by interactions between a particle and the gas
molecules surrounding it. The so-called slip correction accounts for these inter-
actions. If a particle is smaller than the mean free path of the gas molecules this
correction is substantial. It decreases, however, for increasing particle size and
becomes negligible far particles much larger than the mean free path of the gas
molecules. In consequence, no correction has to be applied for estimating the
transport of particles larger than 1 µm in diameter.
Considering a sphere of unit density, ρo, and diameter, dae, for which (ρo-
dae2) = (ρd2), its transport properties are identical with those of all particles char-
acterized by the same value of (ρd2). Its diameter is called the aerodynamic
diameter. The behavior of this fictitious sphere is representative of all particles
collected with the same efficiency by the respiratory tract regardless of their den-
sity. Or, in other words, this sphere represents all these particles as far as their
transport properties are concerned. However, it does not represent them as far as
their physical properties are concerned (particle diameter, particle density, and
consequently particle mass).
For each monodisperse aerosol with spheres of 0.9 and 3.2 g cm–3 density
used to study deposition of the respiratory tract, the aerodynamic diameter can
be calculated by
dae = d (ρ/ρ0)0.5
and total deposition can be plotted as a function of their aerodynamic diameter.
For both flow rates, deposition is an unique function of the aerodynamic diame-
ter (Fig. 7, bottom) and thus the concept of the aerodynamic diameter obviously
applies to particle behavior in the human respiratory tract.
D. Limitations of the Concept of Aerodynamic Particle

Diameter
This concept is confined to particles transported by gravitational sedimentation

without interference of diffusion and, consequently, to particles larger than 1 µm
in aerodynamic diameter. For smaller particles an aerodynamic diameter is not
defined. Therefore, the abcissa in Fig. 7 (bottom) has to have a 1-µm origin.
Since both gravitational and inertial transport are dependent on (ρd2), the
aerodynamic diameter concept also applies in principle to inertial transport of
particles larger than 1 µm in aerodynamic size. Inertial transport contributes to
particle deposition in the human respiratory tract for particles larger than 2 µm in
aerodynamic diameter. Therefore, particle deposition for spheres of different
density is an unique function of the aerodynamic diameter.
Very often inertial deposition in impactors is used to characterize the aero-
dynamic behavior of aerosol particles. However, much larger inertial forces are
applied for particle deposition in impactors than are available for particle deposi-
tion in the human respiratory tract. The particle size obtained by this technique is
the “inertial diameter.” This diameter is defined in the same way as the aerody-
namic diameter but based on inertial rather than gravitational particle transport.
When a particle is not only inertially but also gravitationally transported its iner-
tial diameter is identical with its aerodynamic diameter.
Even ultrafine particles which are solely deposited in the lungs by diffu-
sion can be classified with impactors. The inertial sizes of these ultrafine parti-
cles are however not suitable for estimating particle deposition in the respiratory
tract. For instance, a 0.05-µm sphere of 3 g cm–3 density behaves in the lungs like
a 0.05-µm particle. However, its inertial diameter is about 0.09 µm.
It must also be recognized that when only the aerodynamic diameter of a par-
ticle is known, its deposition efficiency in the respiratory tract can be estimated but
it remains unknown what mass this particle delivers to the surfaces of the respira-
tory tract. This mass can be estimated only when either the density or the geometri-
cal diameter of this particle is known. For instance, the mass of spheres that are 2
µm in aerodynamic size decreases by more than a factor of 5 when their density in-
creases from 0.1 to 3 g cm–3 (Table 1). Although the particles are deposited with
equal probability in the human respiratory tract, the mass they deliver to airway and
airspace surfaces is far from being equal. For all spheres of equal aerodynamic size,
the sphere with the lowest density carries the greatest mass into the lungs.
E. Intersubject Variability
Total deposition varies considerably among healthy individuals breathing

monodisperse aerosols with identical pattern (Fig. 8). This huge variability is de-
termined by the intersubject variability of airway and airspace morphometry.
Table 1 Mass (m) of Spheres of Equal Aerodynamic

Diameter (dae) but Different Density (ρ)
dae (µm) 2.0 2.0 2.0
ρ (g cm-3) 0.1 1.0 3.0
d (µm) 6.3 2.0 1.2
m (pg) 13.1 4.2 2.4
1.0
0.8
Total deposition
0.6
0.4
0.2
0.0
1 3 5 7
Figure 8 Total deposition of spheres 1, 3, 5, and 7 µm in diameter and 0.9 g cm3 den-
sity in the respiratory tract of 20 healthy individuals breathing the aerosols orally with 4-s
breathing-cycle period and flow rate of 400 cm3 s–1 from functional residual capacity.
Airway and airspace dimensions of these individuals estimated from deposition

of 1-µm particles due to gravitational transport during end-inspiratory breath-
holding are closely correlated with the total deposition of the individuals. The
respiratory tract of individuals with wide airways collects particles less effi-
ciently than that of individuals with narrow airways.
This huge intersubject variability of particle deposition has serious conse-
quences for the therapeutic application of aerosols: monitoring the inspired mass
of a drug is not sufficient; monitoring the deposited mass of the drug is neces-
sary. A safe aerosol therapy with drugs of narrow therapeutic width requires
therefore individual dosimetry.
V. Regional Deposition
A. Experimental Methodology
Determination of regional deposition is usually based on measurements of particle

removal from the respiratory tract after short-term steady-state breathing of radio-
labeled particles relatively insoluble in body fluids. First of all, total deposition can
be partitioned into extrathoracic and thoracic components by external detection of
the amount of radiotracer deposited in head and neck and in thorax immediately
after particle administration with a number of scintillation detectors placed around
head or thorax as schematically shown in Fig. 9. Thoracic deposition can then be
Figure 9 Scheme of the scintillation device for determining the amount of radiotracer
deposited in head, neck, and thorax. The configuration of scintillation detectors and
shielding allows detection of particle removal from the thorax regardless of the spatial
distribution of particles within thorax and stomach.
partitioned into a bronchial and an alveolar component by external detection of the

amount of radiotracer retained in the thorax over a couple of days after particle ad-
ministration (Fig. 10). During this time the thoracic activity decreases in two dis-
tinct phases: a fast phase, complete within 40 h, due to mucociliary transport of
particles to the glottis and subsequent swallowing of the particles, and a slow
phase due to macrophage mediated particle removal from the thorax. The activity
removed by mucociliary transport from the thorax is associated with particles de-
posited on surfaces of ciliated airways and that removed by macrophages with par-
ticles deposited on surfaces of nonciliated airways and airspaces. This radiotracer
technique is confined to particles larger then 0.1 µm. Its sensitivity is not sufficient
for studying regional deposition of ultrafine particles.
It has recently been recognized that a fraction of particles deposited on sur-
faces of ciliated thoracic airways is not removed from these airways within 40 h
but retained for longer periods (4). This long-term retention phenomenon was
observed for particles smaller than 6 µm in diameter. Although particle removal
from thoracic airways is therefore overestimated by the radiotracer technique, it
affects bronchial deposition by less than 10%.
B. Effect of Fluid Dynamics
When an aerosol enters the respiratory tract, its particles first experience inertial
transport onto airway surfaces in the extrathoracic and upper bronchial region.
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Volume I, No. 9, September 1911
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Title: The Review, Volume I, No. 9, September 1911
Author: Various
Publisher: National Prisoners' Aid Association
Release date: February 12, 2024 [eBook #72941]
Language: English
Original publication: New York: National Prisoners' Aid

Association, 1913
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*** START OF THE PROJECT GUTENBERG EBOOK THE REVIEW,

VOLUME I, NO. 9, SEPTEMBER 1911 ***
VOLUME I, No. 9. SEPTEMBER, 1911
THE REVIEW
A MONTHLY PERIODICAL, PUBLISHED BY THE
NATIONAL PRISONERS’ AID ASSOCIATION
AT 135 EAST 15th STREET, NEW YORK CITY.
TEN CENTS A COPY. SEVENTY-FIVE CENTS A YEAR
E. F. Waite, President. James Parsons, Member Ex.

Committee.
F. Emory Lyon, Vice President. A. H. Votaw, Member Ex.
Committee.
O. F. Lewis, Secretary and G. E. Cornwall, Member Ex.
Editor Review. Committee.
E. A. Fredenhagen, Chairman Albert Steelman, Member Ex.
Ex. Committee. Committee.
PRISON LABOR LEGISLATION OF 1911
By E. Stagg Whitin
General Secretary, National Committee on Prison Labor
The state’s property right in the prisoner’s labor exists by virtue of

the 13th Amendment of the Constitution of the United States which
provides that slavery or involuntary servitude may be a punishment
for crime, after due process of law. This property right the state may
lease or retain for its own use, the manner being set forth in state
constitutions and acts of legislatures. To make this of material value
the prisoner’s labor must be productive. The distribution of the
product of the prisoner’s labor inevitably presents the problem of
competition. The confounding of the evil of penal servitude with the
methods of production and the methods of distribution which have
grown out of it has produced a confusion in the thought underlying
prison labor regulation by legislative enactment.
The usual penological analysis of prison labor into lease, contract,
piece-price, public account and state-use systems is impossible to
use in an economic analysis of the labor conditions involved.
Economically two systems of convict production and two systems of
distribution of convict-made goods exist; production is either by the
state or under individual enterprise: distribution is either limited to
the preferred state use market or through the general competitive
market. In the light of such classification the convict labor legislation
of the current year shows definite tendencies toward the state’s
assumption of its responsibility for its own use of the prisoner on
state lands, in state mines and as operatives in state factories; while
in distribution the competition of the open market, with its
disastrous effect upon prices, tends to give place to the use of labor
and commodities by the state itself in its manifold activities.
Improvements like these in the production and distribution of the
products mitigate evils, but in no vital way effect the economic
injustice always inherent under a slave system. The payment of
wage to the convict as a right growing out of his production of
valuable commodities is the phase of this legislation which tends to
destroy the slavery condition. Such legislation has made its
appearance, together with the first suggestion of the right of choice
allowed to the convict in regard to his occupation. These statutes
still waver in an uncertain manner between the conception of the
wage as a privilege, common to England and Germany, and the
wage as a right as it exists in France. The development of the idea
of the right of wage, fused as it is with the movement towards the
governmental work and workshops, cannot fail to stand out in
significance when viewed from the standpoint of the labor
movement.
The expression of these tendencies found in the legislation of
1911 comes to view in divers states and a confusion of statutes in
which every shade of development is present. While no state
legislated to give new powers of leasing or contracting for the labor
of prisoners and one only, Idaho, extended the field of its present
leases, twenty-one made some provision for the state’s assumption
and operation of industries: eight, California, Idaho, Indiana,
Missouri, New Jersey, North Dakota, Ohio, and Wyoming, provided in
some manner for the state’s consumption of the manufactured
articles; and six, California, Indiana, Missouri, New Jersey, Ohio, and
Wyoming, established laws for the regulation of prices and
standardization of commodities. The prisoner received compensation
for labor in six states, Florida, Kansas, Michigan, Nevada, Rhode
Island, and Wyoming; his dependent family was given assistance in
five, Colorado, Maine, Massachusetts, Missouri and New Jersey;
while Nevada gave him the right to choose between working on the
roads or working indoors. The New York farm and industrial colony
for tramps and vagrants is of significance. Florida met the peonage
issue by a provision for working off fines during imprisonment. The
antagonism of organized labor to the distribution of the products of
the convict’s labor on the open market resulted in the passage in
Montana, Oregon and California of laws requiring branding of convict
made goods. The New Jersey and Wyoming laws, which are
especially complete, are summarized below.
In a word, the economic progress in prison labor shown in the
legislation of 1911 is toward more efficient production by the
elimination of the profits of the leasee, more economical distribution
by the substitution of a preferred market where the profits of the
middleman are eliminated in place of the unfair competition with the
products of free labor in the open markets, and finally the
curtailment of the slave system by the provisions for wages and
choice of occupation for the man in penal servitude.
New Jersey.—The sale on the open market of the products of
convict labor of any state penal institution is prohibited after the
expiration of existing contracts. A preferred market is established
consisting of all manufacturable articles consumed by the state and
sub-divisions thereof. A prison labor commission is created to so
regulate the penal industries that the greatest amount consumable
by this preferred market will be produced. They are to publish a list
of all possible articles of manufacture and grant releases when
articles cannot be supplied. Penal officers are required to keep all
physically capable convicts employed, not to exceed nine hours a
day except Sunday and holidays, on productive work or in receiving
industrial and scholastic instruction.
Yearly budgets are to be sent on October 1st to the commission
by all purchasing officials in the state. The penal institutions are to
report fully regarding all convict labor and its productive power
together with the cost of production. A uniform system of accounting
is to be established, together with a standardization of commodities
to be manufactured, on which is to be affixed a fair price.
Agricultural pursuits are to be given preference and the products
sold as above, except that the surplus products may be sold at
advertised auction to the general public once in six months unless
they are of destructible character and require more immediate sale.
Counties and municipalities are to conform to the state plan but may
employ the prisoners for their own use. Charitable institutions are
allowed to manufacture for their own use. Prisoners’ families
dependent on charity are relieved by the commissioner of charities
at the rate of fifty cents for every day the prisoner works, but this
relief fund is limited to 5 per cent. of the value of all goods
produced. The services of charitable societies are to be used for
making investigations of families. The estimates of added
appropriations needed to carry this into effect are to be included in
annual estimates. The commission reports to the governor.
Wyoming.—The state board of charities and reform and the
warden constitute a state commission on prison labor, to regulate
according to its best judgment the employment of the state convicts
so that they may acquire a knowledge of a trade at which they can
earn a livelihood upon release. The labor of the convicts is to be
upon products for the state and sub-divisions of the state, and public
officials cannot purchase in the open market, unless upon release by
the commission. The price is fixed at the market price, and the type
of articles may be standardized. Prisoners, in the discretion of the
commission, are to receive a graded compensation, in no case more
than 10 per cent. of earnings of the institution. Surplus earnings
may go to a prisoner’s family, but may never be used in buying food
or clothing beyond that of common usage in his class; the balance,
paid on release, is subject to draft.
A REAL JAIL
[From the Boston, (Mass.,) Globe, August 6, 1911]
The new jail and house of correction for Plymouth county is the
finest of its kind in the state. To Sheriff Henry S. Porter credit is due
for the jail. Had it not been for his untiring efforts to get the county
commissioners to buy and build in this locality the county would not
have had such a place.
Soon after the county purchased the property work was
commenced on laying out for the new building. Excavating began in
1907. The work was done by the “trusty” prisoners, in charge of
officers and engineers. The building is fireproof. The material is
concrete and iron, most of the work being done by the prisoners
themselves. All the floors in the institution are of terrazzo, made and
finished by the “trusties” after a few instructions. Such a building put
out to contract would have cost Plymouth a fortune, more than
$200,000, but as it is the cost will not be far from $100,000.
The jail is on the top of a hill. It commands a view of the
surrounding country. It has a frontage of 250 feet, and is 48 feet
deep, with an ell 86×46.
In January, 1902, when Sheriff Henry S. Porter took the position
of high sheriff of Plymouth county, there were 53 inmates in the jail.
During the following five years prisoners increased to nearly 100. At
the present time the number varies from 120 to 130. After he had
been in office a short time he began to consider improvements for
the men. They were all cane-seating chairs for townspeople, an
industry which netted the county but $400 a year and they paid an
instructor $1200. The sheriff found that a good man who had some
experience could earn only about five cents a day and others two
and a half cents and that the industry was not a paying one. It was
then that he first devised the plan of working his men in the open.
He hired half an acre of land in Samoset street and placed four or
five of the “trusty” prisoners, in charge of officers, tilling the ground.
That year he raised 50 bushels of potatoes, and the men who did
the work were in much better condition than those employed inside.
The sheriff was vigorously opposed by the county commissioners,
who ordered him to stop the work, but after he had shown what
could be done the commissioners decided to let him continue. A
tract of land of three acres was bought in 1904, and that year the
sheriff raised 519 bushels of potatoes, 265 bushels of turnips, 610
pounds of ham, 325 pounds of rib and at the end of the season had
four hogs left. The products sold for $1084.25. The expenses were
$390. They were for dressing, seed and tools.
The next year the sheriff made more money, and provided fresh
vegetables and potatoes during the winter for the men in the
institution. In 1907 he prevailed upon the county commissioners to
purchase what was known as the Chandler farm, at Obery, about a
mile from the center of Plymouth on which was a dwelling house
and barn. Its acreage was 135, field and woods. The farm was much
run down and was covered with bushes and weeds. The sheriff
started in immediately to build it up, and a large number of the
“trusty” men were put out there, with officers in charge, and cleared
away the bushes and broke up the land. Part of the men worked on
the new jail, while the others were employed in the garden.
In 1910 about 15 acres were broken up into tillage land. In that
year was grown 75 tons of hay, 175 bushels of potatoes, 850
bushels of turnips, 650 bushels of corn, many vegetables, five tons
of cabbages, 100 hogs, scores of sheep and numerous hens. At the
beginning of 1911 there were five cows, two yokes of oxen, seven
horses and a large number of hogs and poultry at the place.
The construction of the new jail was begun late in 1908, and
since then an average of 48 to 50 men have been employed at it
daily. A good deal has been said about the care and expense of
prisoners in all institutions, but Sheriff Porter believes that his
scheme is one of the best that can be done for prisoners, as the
work benefits the men and they are not likely to come back. Last
year the sheriff had to send to the state farm for men to assist in the
general work. Out of 100 who have been here and worked on the
farm, 85 have made good. The sheriff believes that good treatment
and outdoor work has good and lasting effects. One man who did
work at the jail for nearly a year after his term expired was
employed by the contractor, and worked every day thereafter until
the building was completed. Several others who worked on the
construction of the building have been working at the concrete
business out in the free world ever since.
“Men who work on the farm have to have different food from
those inside,” says the sheriff. “We give them a hearty breakfast,
dinner and supper and no fault is found with the bill of fare.”
During the period of outdoor work only four men have tried to
escape. They were brought back. Not a man has been treated
roughly and no man has been required to do more than a fair day’s
work. The sheriff says that when he first took charge the dungeon
was used 65 times a year. Last year it was only used three or four
times, which seems to show that the prisoners are contented.
THE EVILS OF “DOUBLING UP.”
On his return from a two-months’ trip to Europe, where he visited
some two-score prisons and correctional institutions, O. F. Lewis,
general secretary of the Prison Association of New York, has raised the
issue in New York City of the “doubling-up” of prisoners in cells. In an
open letter, published in interview form in several city papers, Mr. Lewis
says:
“I have just returned from a two months’ visit to about forty

prisons in Belgium, Holland, Germany, England, and Scotland. In not
a single cell of the thousands which I saw did I see two inmates
imprisoned. One might say that the first principle of all in
administering correctional institutions in Europe and in Great Britain
is that prisoners shall never be ‘doubled up.’
“As for the situation in New York city on the night of September
10, at the Jefferson Market district prison, in four cells two men were
sleeping, though only one cot was in each cell. In two instances the
men were sleeping, one at the head and one at the foot of the cot;
in two other instances, one of the men was sleeping on the floor.
The ‘doubling up’ was occasioned by a lack of cell space for the male
prisoners. On the ground floor there is for male prisoners a pen with
bare boards, not separated off into bunks, where men sleep or try to
sleep overnight.
“In the night court for men on East Fifty-seventh street the prison
connected with the court was so crowded at 11.30 on that night that
in several cells five and six men were confined, so closely as to
forbid any of the men lying down unless on the floor. In one large
room sixteen peddlers, fined $2, were awaiting midnight to pay $1
then remaining of their fine. The night keeper at the district prison
stated that the prison is frequently grievously overcrowded, that
‘doubling up’ of three or four persons is common, and that on such
nights as last night it is necessary to pack prisoners into the various
cells and await the close of court, when the distribution can take
place with some alleviation, but with a continuance of the ‘doubling
up’ system.
“At the Criminal Courts building there are so-called prison pens in
which persons not yet convicted are held often for hours pending
their appearance in some one of the parts of the Court of General
Sessions. Particularly on Fridays one of these pens, smaller than the
cattle car of a freight train is packed with from fifty to seventy-five
persons, mainly young men. No more improper or wretched
preparation for a court trial could, it seems to me, be imagined than
this pen. Fortunately our foreign visitors to the International Prison
Congress last fall were not shown this pen. Grand juries and the
Prison Association have since the first of the year frequently called
the attention of the borough president to this condition, yet it
remains unchanged. ‘Doubling up’ is of frequent occurrence in the
Tombs. English law expressly provides that such ‘doubling up’ shall
never take place.
“We cast around for explanations of crime waves, increasing
tendency to criminality, and a growing disregard by young men in
New York City of the principles of law and order. I fail to see how
any young man going through the experience now daily undergone
by hundreds of our young men can emerge from New York City’s
prisons without a vindictive attitude of mind toward the city which
maltreats him thus.
“The remedy is more money—more money for more cells and
more prisons. For some years a new workhouse has been
contemplated. It is as necessary to have an up-to-date workhouse
as an up-to-date police force. If we are to have a night court for
men, to save the innocent from overnight imprisonment, we must
have a night prison which will not condemn the guilty to intolerable
conditions of imprisonment. If we expect to reform our young
criminals, we must provide a cell for each prisoner. And if the city is
really concerned with the reduction of crime, its Board of Estimate
and Apportionment must clearly recognize that it costs money to
reduce crime, and that one of its first principles of useful
imprisonment is separate confinement.”
DOMESTIC RELATIONS COURT OF NEW YORK
By Kellogg Durland
[Reprinted from Boston Transcript]
The domestic relations court which was established in New York

city exactly one year ago has already taken its place as a permanent
institution of the city. The tremendous work of this court arouses
wonder that the idea had not been adopted years ago and that it is
not more widely emulated in other cities throughout the country.
Chicago and Washington are the only two other cities where similar
courts exist, and even in these cities the jurisdiction of the courts is
not quite the same as in New York. There are two domestic relations
courts in New York city, one located in East Fifty-seventh street in
the same building with a magistrate’s court and a municipal civil
court, and serving the needs of the residents of the two boroughs,
Manhattan and the Bronx; the other is in Brooklyn, administering to
that section of the greater city.
The domestic relations court is essentially a poor man’s court. In
its prime office, indeed, it partakes of the nature of a conciliatory
court, similar to the conciliatory courts of France, through which all
domestic difficulties pass before any divorce or other serious case
involving domestic infelicity, abandonment or non-support can enter
the courts proper. Like the judges of the conciliatory courts in
France, the judges of the domestic relations court in New York are
chosen for their tact, patience, knowledge of mankind and sympathy
with the frailties of men and women. Every case that comes into the
domestic relations court these judges first try to adjust without legal
procedure.
In the next instance the domestic relations court is a woman’s
court. In almost every case that has appeared here the complainant
has been a woman. It is not more than once in several months that
a man appears as a complainant in this court. This is, of course,
largely owing to the fact that man is not usually dependent upon his
wife for support, and even if deserted by his wife a man is not likely
to be exposed to hardship and suffering as is the case with a
woman. Furthermore, this court has no power to grant divorces. It
merely adjusts differences, punishes abandoning husbands, and
advises separation when separation seems the only wise course, and
determines the amount of money that the man must contribute
towards the support of his wife, children or other relatives. The law
under which the domestic relations court was established provides
that to this court “shall be taken or transferred for arraignment,
examination or trial, or to which shall be summoned all persons
described as disorderly, all persons compelled by law to support poor
relatives, and all persons charged with abandonment or non-support
of wives of poor relatives under any provision of law, conferring
upon magistrates summary jurisdiction or the authority to hold for
trial in another court.” The law further provides that “the
commissioner of public charities shall establish and maintain an
office of the superintendent of outdoor poor in or convenient to the
building in which is situated the domestic relations court.” This latter
provision is to insure the supervision over delinquent husbands and
also to provide against any miscarriage of support money. In other
words, it is a sort of clearing house and controlling office after the
case has passed through the domestic relations court.
The functions of the domestic relations court in New York,
therefore, are clearly defined and extremely limited. In Chicago the
domestic relations court has a much more ample scope, for it has
jurisdiction in any of the following violations of state laws: Abduction
of children under twelve years of age, abandonment of wife or child,
bastardy, improper public exhibition or employment of children under
fourteen years of age, contributing to dependency or delinquency of
children, violation of all laws relating to child labor, violation of all
laws relating to compulsory education and truancy, climbing upon
cars by minors, permitting minors to gamble in saloons, permitting
minors to enter dance halls where intoxicating liquor is sold, sale or
gift of deadly weapons to minors, having or procuring intoxicating
liquors for minors, sale of tobacco to minors. And also the Chicago
court has jurisdiction over violations of the following city ordinances:
sale of cigarettes to minors, sale of cigarettes within 600 feet from
schoolhouse, gathering of cigar refuse by minors, sale of tobacco to
minors under sixteen years of age, sale of intoxicating liquors to
minors, purchasing of intoxicating liquors by minors, obtaining
intoxicating liquors by minors by false pretences, sale of materials
saturated with liquor to minors under sixteen years of age, giving
samples of intoxicating liquors in bottles or otherwise to minors,
gambling by minors in saloons, jumping up on moving cars by
minors under eighteen years of age, employment of minors under
sixteen years of age in pawnshops, receiving pledges from minors by
pawn brokers, sale of deadly weapons to minors. Thus it is apparent
that the Chicago domestic relations court is almost a combined
children’s court. If the jurisdiction of the New York court were
anything like as large, the calendar would be constantly glutted, and
cases would have to wait as long as cases on the Supreme Court
calendar must needs wait now. As it is, the domestic relations court
handles all of its cases promptly, although it is perhaps the busiest
court of the city, owing to the fact that the docket is cleaned up
every day.
The two judges who sit in the Manhattan court are Magistrates
Harris and Cornell. Each magistrate sits fifteen days alternately, then
five days in one of the regular criminal magistrate’s courts, and then
ten days holiday. Under Judge Harris and Judge Cornell the domestic
relations court experiment has been tried out and proved successful.
Under these two magistrates there has been established a
progressive procedure in regard to husbands who refuse to live with
and support their wives and families. When a woman appears in this
court the judge listens to her story and if he feels that there is
ground for action or need of legal interference, he will issue a
summons which is really a legal form of request to the husband to
appear in court on a certain day. The wife is then told to come back
on the same day. If the husband appears in response to this
summons, all well and good.
On the other hand, if he fails to take cognizance of the summons,
a warrant is issued for his arrest, and he is brought to court willy
nilly. When the moment for trial comes, the woman is put on the
witness stand and after being duly sworn, proceeds to tell her story,
without let or hindrance. If the corporation counsel happens to be
present he represents the woman, and the defendant is entitled to
counsel, although most of them are willing to tell their side of the
story and abide by the decision of the judge. In the absence of the
corporation counsel the presiding magistrate questions the woman,
not in a hostile way at all, but with the idea of drawing from her all
the facts which shall enable him to attain a wise decision. When she
has finished the defendant takes the stand in the usual way and the
judge questions him with a similar desire to elucidate the trouble. If
the case is flagrant it is within the power of the court to sentence
the man to the workhouse for a period of not more than six months.
Many women urge that their neglectful husbands be sent away, but
it is in this connection that the law is perhaps not all that it should
be. If sending a man to prison provided his wife and children with
bread and butter and rent it might frequently be a good thing for
society in general and the family in particular to have the man
locked up. Unfortunately, a man sent to Blackwell’s Island for six
months is obliged to do work for the state, but this precludes all
possibility of his contributing to the support of his family during the
period of his incarceration. Furthermore, the law will not allow the
prosecution a second time of a man who has just served a term of
imprisonment for non-support or abandonment within one year of
the first prosecution, so that if a woman asks the court to lock up
her husband and the court complies, that woman voluntarily
surrenders all legal right to take further action against him or collect
money from him for a whole year. There is an agitation just now to
have the state pay a prisoner for the work he does during his term
of imprisonment and have the money forwarded to his family. This
surely is a wise and reasonable provision.
If the court stipulates that a man making nine or ten dollars a
week must contribute three dollars and a half or four dollars a week
to the support of his family, that man is either placed on probation
to one of the two regular probation officers attached to the domestic
relations court, or he is placed under the supervision of the
department of charities, alimony division. Money to be paid through
the department of charities is regulated in this way. The defendant is
instructed to bring or send the stated amount to the office of this
department, at the foot of East Twenty-sixth street, a certain day in
the week, and then the wife or whoever is to receive the money
must call in person the following day and, upon accepting the
amount, is required to give a receipt which is duly sent to the
remitter. These receipts often figure in court at a later date as
evidence of the amount of money which has actually been paid by
the payee. It frequently happens that a man will contribute faithfully
for several weeks and then payments will cease. In some instances
this secession of payment is for a legitimate reason—the man may
be sick, or may have lost his position, whereupon he is given an
opportunity to explain in the court the reason for his delinquency.
When the wife appears in court and tells the magistrate that her
husband has become delinquent, the clerk of the court sends out a
printed form which reads as follows:
Dear Sir—I have been informed by your wife, So-and-So,
that you have failed to comply with the direction of the court
to pay her——so much——per week. I desire to inform you
that unless the direction of the court is complied with at once,
a warrant will be issued for your arrest and you may be
compelled to furnish a bond to insure the payment of the said
money for the support of your family.
Respectfully,
If the man appears in court in response to this notice, all well and
good, otherwise he is arrested by an officer and brought before the
judge to explain his failure to comply with the direction of the court.
The work of the domestic relations court is constantly increasing
as the functions of the court are being more widely heard of
throughout the city, especially among the foreign population. The
largest number of cases that come before this court are classified
under the nationality of Russia. There is an injustice in this
classification, however, inasmuch as the “Russians” are 99 per cent.
Russian or Polish Jews. Very many of the cases brought by the
Jewish women are extremely difficult to handle owing to the fact
that the desertion has oftentimes taken place in Europe. A man
living in the ghetto of Warsaw or Bialystok or Wilna will decide to
come to America to seek his fortune. Not having money enough to
bring his wife and family, he starts out alone leaving behind him the
assurances that he will return for them, or will send them money to
bring them over. As a rule two or three letters at least are sent back
to the old country, containing money orders for little sums of money,
then the letters will cease. Sometimes the wife waits for four or five
or six years before in despair she sets out in quest of her husband.
Sometimes she finds him married to some American woman or some
woman he has met over here, and then she goes to court with her
trouble. The law here is confronted with the situation obviously
impossible to handle with equal justice to all parties concerned
without working hardship somewhere. The wife from the Old World
with her children certainly has first claim upon the man, but at the
same time the wife whom he has married here has perhaps married
him in good faith, knowing nothing about the other family, and so
have her children been born.
The Italians are the second largest nationality in the classification
of the domestic relations court cases. The Italians are very apt to be
disorderly persons. They are hot tempered, quick to strike and a
great many times an Italian wife appeals to the domestic relations
court because her husband has been cruel to her and struck her, and
this court is obliged to send her to the magistrates court in order
that her husband may be treated as a disorderly person. In justice to
the Italians of Northern Italy, it should be stated that it is very rare
to find an Italian in the domestic relations court who originally came
from any province in Italy north of Rome. The great mass of Italians
who get into this court are Neapolitans, Calabrians and Sicilians. The
third group are from Central Europe, Hungarians, peoples from the
Balkan states, Galicia and other provinces of Austria. The French
rarely are obliged to appeal to the domestic relations court. The
French are naturally a home-loving people, and anything like a
domestic break is rare among them. Only two or three times since
this court was established have French couples been obliged to
appear there. A great many people classify themselves as Americans
when as a matter of fact they are foreign born, so that the figures in
regard to the number of Americans in this court are misleading.
Negroes, however, turn up here in great numbers. Colored men
often have no sense of responsibility whatever and they are
constantly forsaking their wives and families or going off with
somebody else’s wife. The excuses offered by colored men who are
haled into this court are often very amusing.
For the most part, however, this is not an amusing court. The
long line of people who press before Judge Cornell and Judge Harris
day after day, is for the most part a sordid, hideous line, and the
tales the complainants tell fill one with contempt and sourness
toward humanity. The domestic relations court offers an even
seamier picture of life in this city than the magistrates courts. While
it is true that occasionally a family of the better class makes appeal
to this court, for the most part the clients are illiterate and very poor.
A very large per cent. of the cases that are brought here are people
who, if abandoned, would become public charges. That is why the
state interests itself to the extent of providing a counsel for
complainants, in order to protect itself from the burden of caring for
helpless women and little children, whom some individual has simply
deserted. There are people who pretend to find amusement in the
rehearsal of the marital woes of the poor. To be sure, occasionally a
case turns up with its funny side, but to me the recitals are
heartbreaking and dreary.
In the state of New York the failure of a man to support his wife,
if there are no children, the crime ranks as a misdemeanor, and six
months in the workhouse is the maximum penalty which can be
imposed upon him. The domestic relations court, in specializing on
this phase of law, will undoubtedly lead to certain reforms and
amendments to the existing law tending ultimately to develop a
system of domestic relations jurisprudence. It is a great boon, as it
stands today, to suffering poor women. Any woman without a dollar
in the world can walk into the domestic relations court, tell her
troubles to the clerk of the court, and then if her case is a worthy
one, she is within a few minutes placed on the witness stand, where
she can repeat the recital to the judge. The whole proceeding of
bringing her husband to the bar of justice and getting the court to
forcing him to provide for her is speedy and absolutely without cost.
A woman under our present system of life ought to have a court of
this kind in which she may take refuge, because the world at large
is, at the present time, so unfair to women. A woman can serve a
man for years, bear him a large family of children, and suddenly be
deserted and left with the burden of support for herself and family
on her. If her husband is faithless, all she can do is to appear before
the supreme court and apply for a divorce, but in this domestic
relations court the judge will make her husband contribute to her
support and to the support of his children.
Drink is frequently at the bottom of domestic troubles, but not
nearly so often as most people would think. Drink, especially
whiskey, frequently makes a man irritable and quarrelsome, which
leads to family rows and frequently to disorderly conduct. The
greatest number of cases that come into this court are against
shiftless, worthless, idle men who seem to belong naturally to the
submerged tenth. One day this week I sat with Judge Cornell for an
entire session of the court and the run of cases which appeared that
day gave ample indication of the tone of the court. One case was of
a colored girl who has been married less than a year, who had
brought her big black husband into the court to explain why he had
abandoned her. The explanation was frankly given. He was so
accustomed to living with white women, he said that he could not
bring himself to live any longer with the wife of his own color. He
was bonded to pay his wife $1 a week. Another woman, neat, pretty
and intelligent, a California girl, not yet twenty, had had her husband
arrested because he insisted that she go on the streets and make
money, not only for herself but for him, as a public prostitute. An
Irish woman complained that her husband who made good wages
drank it all up. He countered by stating, under oath, that his wife
was an habitual drunkard, which made no impression whatsoever on
the court, because the woman was particularly prepossessing and
without a single incriminating mark upon her. There were the usual
number of Jewish women whose husbands had simply gone off
saying they would have nothing more to do with them. And one or
two Italian women, with small babies in their arms, whose husbands
had got angry with them and put them out of the house or struck
them.
It is a miserable, pitiable phase of life that one sees in the
domestic relations court, but that the court is so overworked, so
constantly busy, is justification enough for its establishment and
indication that any large community requires some such institution
to placate and bring together men and women, husbands and wives,
whom oftentimes trifling difficulties are about to separate, and to
make it impossible for husbands to desert their wives with impunity.
That there should be only three such courts in this country is a
striking commentary on the life we lead when it has been proved
and demonstrated so extraordinarily by the domestic relations court
in New York city that the need is so great. A visit to the domestic
relations court will not insure a pleasant afternoon or an amusing
hour, but it will prove an enlightening experience.
IN THE PRISONERS’ AID FIELD
PRISONERS’ AID
WORK IN CALIFORNIA
The San Francisco Post reports that:

“A statement of the work of the California prison commission
during the past year shows that a remarkable number of men and
women, who have been released from prison, have been given
employment by this organization through the good work that is
being accomplished at Golden Rule Hall. At this place those who
have been discharged from prison are provided for until suitable
employment is found for them.
“During the past year 465 have been placed in positions, an
average of nine a week. Of these 26 were over 60 years of age, and
four over 80. Fourteen consumptives were placed either in positions
of light employment or in homes or hospitals. More than 200 were
sent direct from prison to employment; others, who were either
invalids, cripples, or aged, were temporarily boarded at Golden Rule
Hall. Another good office of the commission is to look after the wives
and children of prisoners.
“All of this work has entailed a great deal of expense. The
building and equipment of Golden Rule Hall, to take the place of the
building that was destroyed by fire, has put the organization into
debt. An appeal is being made to the public to lessen this difficulty,
and to help along an institution that is doing much toward
preventing a repetition of crimes by ex-convicts.”
As to the renovation of San Quentin prison, the Post says:
“Within a few months the new 800-room concrete and steel
cellhouse now in course of construction at San Quentin prison will be
completed.
“The building is a prison within a prison, and is a class A
structure, 600 feet in length and 60 feet in height. The cells are built
in the center of the structure and run its full length. There are four
tiers with 200 cells on a tier. Four hundred of these cells are
separated by steel bars and are so arranged that twenty-five may be
bolted at the same time. Eight hundred prisoners may be locked up
three minutes after they reach the inside of the prison.
“The walls and the cells of the new prison are built of reinforced
concrete and in every foot of concrete steel bars are laid, running
parallel and perpendicular, making it impossible for a prisoner to cut
through at any point of his cell.
“All the steel and iron work was turned out by the prisoners.
Every part of the new building was manufactured and erected by
prison labor. The roof of the structure is of copper and slate and has
been pronounced by experts to be of the finest workmanship. The
inside is finished with plaster and so clever is the workmanship that
it resembles enamel work.
“Work is now being done on a wall sixty feet high and six feet
thick by the prisoners. This will surround the cellhouse. Upon
completion an electric light plant and heating apparatus will be
installed.
“Warden Hoyle plans when the new cellhouse is ready for
occupancy to put his new grading system into execution. The new
prison will house all the first termers and they will not mingle with
second and third term convicts. Each grade will have a separate yard
and under the first grade the prisoners will wear a uniform.
“The second termers will be together and wear a different kind of
a uniform. The third grade will consist of life termers and hardened
criminals. These will wear stripes.
“The first-grade prison will be known as the reformatory, and at
any time a prisoner’s deportment is bad he will be sent into the
second-grade prison.”
SUPPORTING A
GOOD WARDEN
The Prisoners’ Aid Society of Baltimore has recently taken up the

cudgels for the retention in office of Charles A. Hook, warden of the
Baltimore city jail. A letter to the mayor of Baltimore details some of
the improvements effected by Warden Hook.
“The citizens of Baltimore have every reason to be proud of this
their one definite penal institution. It has reached an excellence of
administration and a physical condition that place it easily among the
foremost institutions of similar nature throughout the country. The
improvements have been very marked, and from simply a
correctional and detentional institution it has been transformed into
a place of real helpfulness and reformation.
“This state of efficiency is the direct result of the wise, practical
and broad-spirited administration of its warden, Mr. Charles A. Hook.
Warden Hook is a student of criminology. He has taken advantage of
every opportunity to meet the wardens of other institutions and
gathered from these conferences that which would be helpful to his
own administration.
“It is becoming more and more evident that the administration of
a penal institution should be as scientifically based as the
administration of a medical infirmary, and no greater boon can be
conferred for the welfare of the municipality than the removal of this
office from political influence.
“To state concretely some of the very many improvements of this
institution I would name the following:
“The addition of 328 new concrete cells for men and women, with
all modern improvements for hygiene and sanitation.
“New hospital and operating room in the main building.
“A library for the prisoners.
“New hot water system for bathing purposes.
“New beds made especially in the institution for the purpose of
extreme cleanliness.
“New sterilizing plant for infected clothing.
“New baths and clothes rooms for prisoners.
“New four-story workshop, of brick and cement.
“New jail workshop, where articles used by the prisoners are
made.
“The substitution of machinery for the hands of the prisoners in
the bakeshop.
“In the moral features of the institution:
“No official is now allowed to strike a prisoner except in self-
defense.
“All cases of infringement of rules are settled by the warden
himself.
“Dark cells and shower baths for punishment abolished.
“All prisoners have the ear of the warden and he gives every
Sunday morning to visitation and the consideration of personal
requests and grievances.
“Prisoners working in the shops with sentences of three months
or over are allowed one-fourth of their earnings, one-half payable
during confinement and the remainder on release.
“Through the personal interest of the warden and his assistants a
large share of the amount earned by the prisoners during
confinement is paid to their families.
“The definite result of these marked improvements in the physical
condition and the moral and spiritual administration is very apparent
in the number of inmates who are brought to realize the possibilities
of a better life through reformation, and by this specific work the
population of the jail is smaller than it has been in past years.
“Every co-operation and sympathy have been granted the work of
the Prisoners’ Aid Association by Warden Hook and his assistants,
and through this co-operation a splendidly large number of men and
women are being returned to society law-abiding and self-
respecting.”

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a treatment (not cure) of asthma. Of course, today we use pharmacological

Claude Lenfant, M.D.

Jacob Anhøj, M.D. Department of Pediatrics, Copenhagen University Hospi-

Hans Bisgaard, M.D., Ph.D. Professor of Pediatrics, Copenhagen University

Lars Borgström, Ph.D. Senior Experimental Medicine Advisor, AstraZeneca

Andy Clark, Ph.D. Inhale Therapeutics Systems, San Carlos, California

Eric Derom, M.D., Ph.D. Professor, Department of Respiratory Diseases,

Myrna B. Dolovich, P.Eng. Associate Clinical Professor, Department of Med-

Mark L. Everard, M.B., Ch.B., F.R.C.P.C.H., D.M. Department of Respira-

Alison A. Hislop, Ph.D. Reader, Developmental Vascular Biology, Institute of

Michael E. Hyland, Ph.D. Professor of Health Psychology, University of Ply-

Beth L. Laube, Ph.D. Associate Professor, Department of Pediatrics, Johns

Peter N. LeSouef, M.D., M.R.C.P.(UK), F.R.A.C.P. Professor and Head, De-

Chris O’Callaghan, B.Med.Sci., B.M., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D.,

Martyn R. Partridge, M.D., F.R.C.P. Chest Clinic, Whipps Cross University

Søren Pedersen, M.D., Ph.D. Professor, University of Southern Denmark,

Cynthia S. Rand, Ph.D. Associate Professor, Department of Medicine, The

Gerald C. Smaldone, M.D., Ph.D. Professor of Medicine, Physiology, and

Janet Stocks, Ph.D. Professor of Respiratory Medicine, Portex Unit, Institute

Magnus U. Svartengren, M.D., Ph.D. Associate Professor, Department of

Lars Thorsson, Ph.D. Experimental Medicine, AstraZeneca R&D, Lund,

Mika T. Vidgren, Ph.D. Professor, Department of Pharmaceutics, University

Johannes H. Wildhaber, M.D., Ph.D. Department of Respiratory Medicine,

Ashley A. Woodcock, B.Sc., M.D., F.R.C.P. Professor of Respiratory Medi-

Paul Wright AstraZeneca R&D, Charnwood, Loughborough, England

Pieter Zanen, M.D., Ph.D. Department of Pulmonary Diseases, Heart Lung

Introduction Claude Lenfant iii

1. The History of Inhaled Drug Therapy 1

2. Basic Principles of Particle Behavior in the Human

3. Structure and Function of the Respiratory System: Developmental

4. In Vitro Testing of Pharmaceutical Aerosols and Predicting

5. Factors Affecting the Clinical Outcome of Aerosol

III. Patient Preference 146

6. In Vivo Measurements of Lung Dose 173

7. Targeting the Lungs with Therapeutic Aerosols 211

8. Nebulization: The Device and Clinical Considerations 269

9. New Nebulizer Technology 303

10. The Metered-Dose Inhaler 337

Delivered from MDIs 346

11. Propellants 371

12. Spacer Devices 389

XIV. A Spacer for a Dry-Powder Inhaler 411