ARTICLE

Cough Conundrums: A Guide to Chronic

Cough in the Pediatric Patient
Vicki Masson, MD,* Catherine Kier, MD,† Latha Chandran, MD, MPH‡
*Division of Pediatric Pulmonology and Sleep Medicine and
†
Division of Pediatric Pulmonology, Stony Brook University, Stony Brook, NY
‡
Department of Medical Education and Pediatrics, University of Miami, Miller School of Medicine, Miami, FL

PRACTICE GAPS

Cough is a common presenting chief complaint in the pediatric population.

Characteristics of cough that are revealed in either the history or physical
examination can facilitate diagnosis and management.

OBJECTIVES After completing this article, readers should be able to:

1. Manage the common causes of cough, recognizing the underlying

mechanics of coughing.
2. Discuss effective and efficient management options based on gathered
clinical evidence.
3. Review existing guidelines for the management of chronic cough.
4. Identify when subspecialty referral is appropriate.

CLINICAL CASE AUTHOR DISCLOSURE Drs Masson, Kier,

A 12-year-old boy with autism spectrum disorder presents with concerns of pro- and Chandran have disclosed no financial
relationships relevant to this article. This
gressively worsening wet-sounding cough for 3 weeks that is worse at night and commentary does not contain a
clears throughout the day. He was initially evaluated 2 weeks earlier and given discussion of an unapproved/
albuterol for possible reactive airway disease. He denies fevers, exercise limitation, investigative use of a commercial
product/device.
or viral prodrome. On examination he is afebrile, with a respiratory rate of
18 breaths/min, heart rate of 100 beats/min, blood pressure of 100/67 mm Hg,
ABBREVIATIONS
and pulse oxygen saturation of 100% on room air. He appears comfortable. Physi-
cal examination is remarkable for bilateral upper lobe faint expiratory wheezing CF cystic fibrosis
COVID-19 coronavirus disease 19
and right-sided neck swelling. What is the next step in the management of this
CT computed tomography
patient? EVALI electronic cigarette or
vape–related acute lung injury
FEV1 forced expiratory volume in 1
INTRODUCTION
second
Cough is a source of considerable financial burden on the health-care system, GER gastroesophageal reflux
accounting for approximately $29.5 million in annual outpatient visits in the OTC over the counter
PBB protracted bacterial bronchitis
United States. (1) The burden on the individual is equally high, costing care- PFT pulmonary function testing
givers’ time and lost wages, school absenteeism, poor sleep quality, and UACS upper airway cough syndrome

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 sports limitations in those affected. According to Allied children aged 14 to 17 years. (9) Coughing at night occurs in
Market Research, the global “cough remedies market” for 25% of children overall. (9) Despite previous meticulous diag-
over-the-counter (OTC) medicines in the category of cough nostic protocols and investigation tools, 12% to 42% of chronic
and cold is enormous, amounting to an estimated $7.08 cough remains unexplained or refractory. (9) In general, there
billion and estimated to grow to $9.91 billion by 2030. (2) is consensus that coughing for more than 8 weeks requires
Considering the burden on the outpatient setting spe- evaluation. (5)(6)(7)(8) Chronic cough, for the purposes
cifically, an Australian multicenter study found that 75% of this article, is defined as longer than 4 weeks in
of a cohort of caregivers sought 5 or more physician con- duration.
sultations to determine the etiology and treatment for pro-
longed coughing. (3) Furthermore, 14% of these sought 15 PATHOGENESIS OF COUGH
or more consultations. (3) A mean generic pediatric Cough is a powerful and normal protective reflex and is
health-related quality of life score, using the Pediatric both a physiological mechanism for mucociliary clearance
Quality of Life Inventory, was also used in this study, and and an essential component of the innate immune sys-
scores were found to be similar to those with other chronic tem. Healthy children cough 10 to 34 times daily. (10)
illnesses, such as cardiac disease and diabetes. (3) Reassur- Cough may be voluntary or reflex initiated. The 3 phases
ingly, quality of life significantly improved with resolution of cough, namely, inspiration, compression, and expira-
of coughing. (3)(4) tion, are regulated by a sophisticated pathway involving af-
Caregivers often seek to treat disruptive coughing with ferent and efferent arms as well as the central pathway. A
OTC remedies often consisting of multiple ingredients. noxious stimulus sends a signal through the afferent arms
Although caregivers hope for cough resolution by adminis- to the central pathway, which involves the nucleus tractus
tering OTC remedies, OTC remedies mask both the char- solitarius, the brainstem respiratory network (cough cen-
acter and severity of the cough and risk significant adverse ter), the subcortex, and the cortex. The central pathway
effects. through the efferent arms activates the respiratory muscles,
Cough is a natural protective mechanism of the body. larynx, and pelvic muscles. The cough pathway, which ma-
A strong and efficient cough is needed to mobilize secre- tures throughout infancy, is thought to be regulated by a
tions and eliminate foreign entities in the respiratory tract. continuous feedback loop in the afferent arms and the
It is, therefore, important to investigate the underlying cough center (Fig 1). (11)
reason for cough before suppression.
CAUSES OF CHRONIC COUGH
EPIDEMIOLOGY In the following sections we discuss chronic cough: com-
When considering 4 major international pediatric guidelines mon causes (Table 1), uncommon causes (Table 2), and
(American, Belgium, British, and Australian), there are emerging causes (Table 3). Each table lists the diagnosis,
some notable differences for determining the duration of risk factors, clinical presentations, characteristics of the
chronic cough. The American College of Chest Physicians cough, evaluation needed, and ensuing sequelae. The
defines chronic cough as longer than 4 weeks, (5) Belgium most common causes of cough are asthma or asthmalike
guidelines consider chronic cough as longer than 3 weeks, (6) conditions, postinfectious causes, upper airway cough syn-
the British Thoracic Society defines chronic cough as longer drome (UACS), gastroesophageal reflux (GER), and pro-
than 8 weeks, (7) and Cough In Children and Adults, Diagno- tracted bacterial bronchitis (PBB). (12) Age is an important
sis and Assessment, an Australian guideline, considers factor to consider in diagnosing the etiology of the cough.
chronic cough to be longer than 4 weeks in duration. (8) In infants and children younger than 3 years, PBB and
The pediatric age group is also variably defined by age postinfectious causes account for a combined 68% of
(<15–18 years) depending on the guideline considered. The cases. (12) Conversely, these conditions rarely afflict preschool-
general rationale across all guidelines takes into consideration age children (3–4 years old), accounting for only 9% of cases.
the natural process of infectious causes of cough and allows Infectious agents and habit cough predominate in children
for adequate resolution of the expected acute inflammatory older than 11 years and in teenagers. (5)(9)
process. Studies suggest that on average 69% of children re-
port coughing with colds, with minimal differences between Common Causes of Chronic Cough
age groups. (9) Conversely, the prevalence of cough without Asthma. Asthma is overall the most common cause of
colds increases with age from 34% in 1-year-olds to 55% in chronic cough in the pediatric age group. Asthma is also a

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 Figure 1. The phases of cough: 1, rest; 2, inspiratory phase (inspiration with glottis open); 3, compression phase (glottic closure and increasing intratho-
racic pressures); and 4, cough with glottic opening (increased diaphragmatic pressures and expulsion).

multifaceted disease, characterized by chronic airway in- Institute asthma guidelines, referral to a specialist is indi-
flammation and variable expiratory airflow limitation. Key cated when symptoms persist and/or exacerbations occur
signs and symptoms of asthma include wheezing, short- despite appropriate treatment (18)(19).
ness of breath, chest tightness, and cough, which typically Fractional exhaled nitric oxide testing can provide addi-
vary in intensity over time. (13) Cough usually is nonpro- tive information when monitoring asthma control by mea-
ductive and occurs in “coughing fits” or “jags” when suring airway inflammation. This is particularly useful in
facing a noxious stimulus. Chronic cough is often a mani- those with allergic or eosinophilic asthma. This test does
festation of persistent airway inflammation. (13) This inflam- not by itself diagnose asthma, but it can provide additional
mation perpetuates a cycle of airway hyperresponsiveness, information in determining whether the current treatment
airflow limitation, and disease chronicity. Atopy, refers to the plan is objectively effective and whether further tailoring
genetic tendency toward the development of an IgE-mediated of treatment is required to achieve the best results. (20)
response to antigens/allergens. Atopy is the strongest predis- Infectious Causes
posing risk factor for developing asthma. (14) Second- and Viral Upper Respiratory Tract Infections
third-hand tobacco smoke continue to be important prevent- A common manifestation of viral upper respiratory tract infec-
able causes of poorly controlled asthma, and a frequent trigger
tions, as well as viral bronchiolitis, is cough. Uncomplicated
for exacerbation and reduced lung function. (15)(16) Environ-
coughing associated with common viruses typically lasts 10 to
mental triggers such as wild fires, cooking smoke, scented
14 days but can last up to 3 weeks. (21) Prolonged coughing
products, cleaning agents, and perfumes should be evaluated.
beyond this period can occur due to the phenomenon of post-
Asthma is very difficult to diagnose in young children
infectious hypersensitivity (see later herein). Common viral
because the utility of pulmonary function testing (PFT) is
etiologies for an upper respiratory tract infection include
limited. The asthma predictive index has become an in-
rhinovirus (30%–50%), influenza (5%–15%), coronaviruses
valuable tool in providing insight into which infants/pre-
(10%–15%), respiratory syncytial virus (5%), and parain-
schoolers with recurrent wheezing will have asthma at
school age. A positive asthma predictive index score must fluenza viruses (5%). (22)(23)(24)
include recurrent episodes of wheezing during the first
Bacterial
3 years of life and 1 of 2 major criteria (eczema or parental
Bordetella pertussis, although overall not a common cause
asthma) or 2 of 3 minor criteria (allergic rhinitis, wheezing
of chronic cough, deserves discussion because treatment
without colds, or peripheral eosinophilia $4%). (17)
Clinical diagnosis of asthma remains relatively straight- is essential in the acute period for those affected as well as
forward based on the presenting symptoms and the pa- close contacts. In nonoutbreak settings, 32% of prolonged
tient’s response to bronchodilator therapy. PFT performed cough is due to pertussis. (23) Importantly, the diagnosis
by experienced personnel typically shows limitation of ex- needs to be considered even when the classical signs of per-
piratory airflow (represented by a reduction in forced expi- tussis are not present to prevent community spread. (21)
ratory volume in 1 second [FEV1] and/or FEV1/forced vital Cough is characterized as paroxysmal with a terminating in-
capacity) reversed by bronchodilators (FEV1 increased by spiratory “whoop.” In its early stages, pertussis can present
12% after bronchodilator use). Such testing is often nor- similar to the common cold, with the typical cough occurring
mal when the patient is asymptomatic. Per Global Initia- at approximately 1 to 2 weeks. In infants, apnea may be the
tive for Asthma and National Heart, Lung, and Blood presenting sign requiring hospitalization. (25)

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 694
Table 1. Common Causes of Chronic Cough

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ORGAN COUGH
SYSTEM ETIOLOGY PRESENTATION RISK FACTORS EXAMINATION POINTERS EVALUATION SEQUELAE
Pulmonary Asthma Cough, wheeze, exercise Early viral Wheeze, cough, Spastic/dry Allergy testing Airway
causes intolerance, responsive infections in diminished air sounding, remodeling
to SABA, chest pain/ genetically entry responds to
tightness predisposed bronchodilators,

Pediatrics in Review
individuals, cough resolves
environmental with empirical
exposures trial of inhaled
corticosteroids
Infectious Viral Cough, 1/- fever, URTI Sick contacts Variable Wet or dry Nasopharyngeal/ Progression of
symptoms presentation, sputum infection to
wet or dry PCR pneumonia
cough, rhonchi, and/or
rales community
Bordetella pertussis 3 stages: catarrhal, Sick contacts, Paroxysmal cough Cough that spread; disease
paroxysmal, unvaccinated terminates is often self-
convalescent with inspiratory limited
“whoop”
URTI symptoms,
cough, apnea in
infants
Mycoplasma Tracheobronchitis, Sick contact Productive cough, Productive, but
pneumoniae pharyngitis, malaise, exposure wheeze, rales may be absent
fever, cough,
headache
Postinfectious Persistent cough 3–8 wk Unknown Coughing without Often dry Self-resolving
hypersensitivity after viral illness wheeze

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Protracted Chronic cough >4 wk Frequent viral Wet coughing Productive cough, BAL Bronchiectasis,
bacterial illnesses, child wheezing, worse 40% recurrence
bronchitis care attendance, at night rate
tracheomalacia,
bronchomalacia
Upper Chronic Headaches, nasal Chronic allergies, Sinus/facial Often dry, CT sinuses Nasal polyps,
airway rhinosinusitis/UACS congestion 1/– narrow sinuses, tenderness, sometimes diminished
causes discharge deviated nasal congestion productive if quality of life
septum copious nasal
discharge
GI causes Gastroesophageal reflux Choking, gagging, spit- Prematurity, Voice changes, Wet or dry cough, pH probe Failure to thrive,
up around feeding, Developmental upper airway worse in supine monitoring recurrent
neck/body posturing, delay, poor sounds, position wheezing/
regurgitation, truncal tone, wheezing, pneumonia
epigastric or obesity, tachypnea
substernal pain correlation with
feeds

BAL=bronchoalveolar lavage, CT=computed tomography, GI=gastrointestinal, PCR=polymerase chain reaction, SABA=short-acting b2-agonist, UACS=upper airway cough syndrome, URTI=upper re-
spiratory tract infection.
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Table 2. Uncommon Causes of Chronic Cough
ORGAN
SYSTEM ETIOLOGY PRESENTATION RISK FACTORS EXAMINATION COUGH POINTERS EVALUATION SEQUELAE
Pulmonary Retained foreign body History of aspiration, Young age, Focal wheeze or Initially dry, may Flexible or rigid Bronchiectasis
causes coughing with eating, developmental absent breath progress to wet if bronchoscopy to
witnessed or delay, young sounds infected retrieve
unwitnessed inhalation/ sibling
ingestion of food or
nonfood item
Cystic fibrosis FTT, chronic cough, Family history, absent Failure to gain weight, Wet cough productive Sweat chloride, Bronchiectasis, obstructive
recurrent or chronic newborn screen wheeze, rales or of copious thick sputum culture, and progressively
bacterial pneumonia, rhonchi, sinusitis, and sticky sputum bronchoscopy, restrictive lung disease,
chronic sinusitis, nasal nasal polyps chest CT transplant
polyps
Ineffective cough Rhonchi persisting after Neuromuscular Poor truncal tone, Weak cough, MIP and MEP Chronic lung infections,
coughing, weak cough, disease, poor weak breath asynchronous bronchiectasis
recurrent pneumonia muscle tone, sounds, weak breathing
developmental cough
delay, young age,
postoperative
Upper airway Auricular nerve Chronic cough associated Postsurgical, chronic Cough related to ear Dry Laryngoscopy Psychosocial
causes irritation with compression of the allergies canal stimulation/
Arnold nerve obstruction
Vascular rings/slings Recurrent wheezing, Presence of other Dry coughing, Dry Contrast chest CT If not addressed may
coughing anatomical swallowing cause critical airway
abnormalities dysfunction, obstruction
recurrent wheezing

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GI causes Tracheoesophageal Cough after feeds Acquired: tracheal or Wet or chronic dry Barking cough around Chest CT, upper Bronchiectasis, chronic
fistula esophageal cough, temporal feeds endoscopy, or pneumonia
surgeries, relation to eating/ bronchoscopy
Congenital: high-risk drinking
syndromes
Infectious Fungal pneumonia Low-grade fevers, cough, Travel or exposure Spectrum of wheeze, Productive cough Death in
causes environmental exposure history, rhonchi, or rales immunocompromised
neutropenia, depending on
hematologic disease severity
malignancy, HIV,
lung transplant,
prolonged ICU stay
>21 d
Other causes Habit cough Cough without known Anxiety, depression, Clear lungs Honking cough Psychosocial
triggers, not when stress
sleeping or distracted
Mediastinal masses Slow worsening None Mass effect, Dry or wet cough Chest CT, MRI chest Death
lymphadenopathy

CT=computed tomography, FTT=failure to thrive, HIV=human immunodeficiency virus, MEP=maximal expiratory pressure, MIP=maximal inspiratory pressure, MRI=magnetic resonance imaging.

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 Table 3. Emerging Causes of Chronic Cough
COMMON
ETIOLOGY PRESENTATION RISK FACTORS EXAMINATION COUGH POINTERS EVALUATION SEQUELAE
COVID-19 Dyspnea, dry Unknown Normal Dry Unknown
related cough
EVALI Cough, nausea, Vape, especially Normal Dry Noncontrast May self-resolve
dyspnea chest JUUL brand chest CT after vape
pain with cessation,
vape exposure prolonged
dyspnea

COVID-19=coronavirus 2019, CT=computed tomography, EVALI=electronic cigarette/vape–related acute lung injury.

Mycoplasma pneumoniae also is not overall a common and nonallergic rhinitis and chronic rhinosinusitis. Saline
cause of respiratory infection, but because it is both quite sinus rinses can be beneficial. Antibiotics can be used if
treatable and communicable, it also should be considered an acute bacterial cause for sinusitis is suspected, eg, fe-
in the differential diagnosis alongside more common vers, facial tenderness, headaches, or sinus pain. Cough
causes. Presentation includes tracheobronchitis, pharyngi- caused by allergic etiologies improves with intranasal cor-
tis, cough, and, sometimes, wheezing. In general, symp- ticosteroids or intranasal or systemic antihistamines. The
toms are mild, lending to the term walking pneumonia. suspicion of UACS rests on the patient’s ability to report
Cough is often productive but sometimes absent in chil- the presence of mucus dripping along the posterior phar-
dren older than 5 years. (26) ynx. The finding of mucoid secretions at the posterior
Typical bacterial etiologies (Streptococcus pneumoniae, Hae- pharynx or a cobblestoned appearance of the posterior
mophilus influenza) that cause pneumonia generally do not pharyngeal mucosa is suggestive. Often these patients pre-
cause prolonged coughing if adequately treated. The strongest sent with throat clearing or snorting-type coughing. Envi-
predictors of pneumonia in general in children are fever, cya- ronmental history is crucial to identify possible allergic
nosis, and increased work of breathing. Bacterial pneumonia triggers. In these patients, allergy testing may be benefi-
generally is associated with crackles (rales) on chest ausculta- cial, and avoidance of exposure to specific allergens is key
tion, focal chest radiographic findings, chest pain, shortness to management. Empirical use of systemic or intranasal
of breath, fever, productive coughing with possible hemopty- antihistamines with or without a decongestant is both di-
sis, and ill appearance. After appropriate antibiotic use, cough- agnostic and therapeutic. (27)
ing resolves within 2 to 3 weeks. (27) Gastroesophageal Reflux. GER most likely causes cough
Postinfectious Hypersensitivity. Patients who exhibit by stimulation of an esophageal-bronchial reflex and by ir-
coughing more than 3 weeks after the resolution of acute up- ritating the lower respiratory tract by microaspiration. (28)
per respiratory tract infection symptoms may have a postinfec- When GER causes cough, there may be no gastrointestinal
tious cough. This occurs in 1 in 10 children who contract viral symptoms up to 50% to 75% of the time. (28) GER, when
illnesses such as respiratory syncytial virus and rhinovirus. present, plays a significant role in the control of chronic
The chest radiographs are normal, and the cough eventually cough, asthma without allergy, and posterior laryngitis.
resolves on its own. This is thought to be due to extensive in- Twenty-four–hour pH monitoring can help to establish a
flammation and disruption of airway epithelial integrity, mak- temporal correlation between cough and GER and is consid-
ing them sensitive to nonnoxious stimuli, thereby lowering ered to be the most accurate diagnostic method for children
the threshold for cough (Fig 2). (25)(26) with suspected GER. Per the American College of Chest
When postinfectious cough emanates from the lower Physicians guidelines, for children 14 years or younger with
airway, it often presents with an excessive amount of mu- chronic cough in the absence of underlying lung disease,
cus secretion accumulation and cough receptor hyperres- treatment for GER should not be used without clinical fea-
ponsiveness. Antibiotics have no role in the management tures of GER, such as recurrent regurgitation, dystonic neck
of postinfectious cough except in the presence of bacterial or body posturing in infants, or heartburn/epigastric pain in
sinusitis or early pertussis. Although optimal treatment is older children. For those 14 years or younger with symptoms
unclear, the use of inhaled ipratropium may be helpful. and signs, or tests consistent with pathologic GER, treatment
Albuterol has not proven to be better than placebo. (25) with acid-suppressive therapy should be initiated for 4 to 8
Upper Airway Cough Syndrome. UACS, formerly known weeks along with lifestyle modifications, and their response
as postnasal drip, is a broad category that includes allergic reevaluated. (28)(29)(30)(31) Lifestyle modifications include

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 Figure 2. Postinfectious hypersensitivity cough. Following an infectious etiology, the airway becomes more sensitive to cough when exposed to what
was previously innocuous stimulus. Cough should resolve within 3 weeks but can persist to a more chronic state during which it lasts for no more than
8 weeks. URTI=upper respiratory tract infection.

weight loss through diet modification if overweight or obese, el- airway. Typical pathogens include Haemophilus influenzae,
evating the head of the bed while sleeping, and meal avoidance S pneumoniae, and Moraxella catarrhalis. (33)
3 hours before bedtime. Barring improvement with these modi- The cause of PBB is not known, but because it is com-
fication, therapy may be initiated via antacids, proton pump in- monly seen in younger children (<6 years of age), it may
hibitors, or H2 blockers. (32) be due to frequent viral illnesses, which cause airway in-
Protracted Bacterial Bronchitis. The initial definition of jury and inflammation, thereby making it easier for bacte-
PBB comprised a history of chronic wet cough, a positive ria to grow and cause infection. Children who attend child
bronchoalveolar lavage culture for a known respiratory care have been known to be at higher risk for PBB. Those
pathogen, and a clinical response to a 2-week course of with underlying tracheomalacia or bronchomalacia may
oral antibiotics for community-acquired pneumonia. The also be at higher risk because these conditions can lead to
current criteria for diagnosing PBB is largely clinical and trapping of mucus in the airways. (34)
includes a wet cough lasting at least 4 weeks, absence of
other findings to identify another cause of the cough, and Uncommon Causes of Chronic Cough
resolution of the cough with at least 2 weeks of an antibi- Apart from the common causes of cough discussed previ-
otic. (33) Chest radiography may be performed to exclude ously herein, there are uncommon causes of cough that
other causes but often does not show any specific signs of must be considered. Some of these uncommon causes
PBB. If able to perform lung function testing, airway ob- may have “cough pointers,” or features of cough that can
struction without reversibility may be seen. Forty percent of lead to a potential diagnosis. Knowledge of these pointers
all children with PBB will have a recurrence of 1 or more epi- may minimize diagnostic evaluation that may otherwise
sodes. In cases of recurrence, referral to a pulmonologist is delay the diagnosis and treatment.
indicated to perform a flexible fiberoptic bronchoscopy with Despite these pointers, there are times when a diagnosis
bronchoalveolar lavage to obtain lower airway cultures for may still be elusive. In up to 20% of patients with chronic
both targeted antibiotic treatment and airway evaluation. cough, treatments initiated are not curative, (34)(35) leading
Bronchoscopy usually reveals purulent secretions in the the care team to consider more uncommon causes. When

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 contending with idiopathic chronic cough, the challenge and available therapies. Historically, chronic productive
lies in finding the precise mechanism responsible for the cough has previously been a cornerstone sign in this dis-
troublesome sign and/or symptom so that appropriate ther- ease. Newborn screening has been an effective means to
apeutic measures can be initiated efficiently to relieve the make this diagnosis early on, but this is not perfect. Sweat
cough. Some uncommon causes to consider are retained chloride testing and genetic testing can adequately diag-
foreign body, cystic fibrosis, ineffective cough, auricular nose this condition in those with a gamut of signs and
nerve irritation, vascular rings or slings, tracheoesophageal symptoms, notably chronic coughing, failure to thrive
fistula, mediastinal masses, fungal pneumonia, or habit (growth failure), malabsorption, chronic sinusitis, and re-
cough. current pneumonia. If CF is suspected, referral to a pul-
Retained Foreign Body. A history of sudden onset of monologist is essential to facilitate both testing and long-
coughing in an otherwise healthy child without evidence of term care. Long-term prognosis ultimately depends on the
upper respiratory tract infection is highly suspicious for aspi- degree of bronchiectasis that has developed secondary to
ration; however, this history is often absent. (36) The classic recurrent and chronic pulmonary infections. Intravenous
triad of new-onset cough, wheezing, and asymmetrical antibiotic treatment is generally required to treat these in-
breath sounds is seen in only 16% to 40% of patients. (36) fections. Lung transplant and/or death have historically
In general, patients with tracheal foreign bodies present with been the end points to this disease, but the recent develop-
dyspnea and are more easily diagnosed due to acuity and se- ment of CFTR modulators provides hope and optimism
verity of symptoms. (36) Bronchial foreign bodies, which ac- for this disease going forward. (40)(41)
count for 80% to 90% of aspirations, typically are diagnosed Ineffective Cough. Coughing, however natural, may not
later and are more likely to present with partially decreased come easily to patients with surgical incisions, thoracic
breath sounds. Partial obstructions can make the diagnosis trauma, respiratory muscle fatigue, or neuromuscular
elusive, resulting in mistaken diagnosis and treatment for weakness. Mechanisms normally existing in the lower
presumed upper respiratory tract infections, bronchiolitis, bronchioles and alveoli to maintain airway patency include
pneumonia, or asthma. In a child with chronic cough, recur- the mucociliary system, immune system, and lymphatics,
rent pneumonias, persistent croup, or asthma that fails stan- which may become compromised either acutely (postoper-
dard medical therapy, one should always consider a retained ative recovery) or chronically (spinal cord injury). These
foreign body in the differential diagnosis. Generally, chest ra- systems depend on the strength of the diaphragm and in-
diographs are considered the first diagnostic study. Confir- tercostal muscles to generate adequate cough force. When
mation is possible, either in the way of finding the this is lacking, the basic cough cycle is impaired, thereby
radiopaque object or suspecting air trapping, but radiographs creating a nidus of infection in the lower airway via re-
cannot be used to exclude the diagnosis. Most foreign bodies tained secretions. Cough in these patients is, therefore,
aspirated are radiolucent and, therefore, chest radiographs weak and inadequate in clearing secretions. Rhonchi are
are normal in more than 50% of tracheal foreign bodies and often heard in the chest after a maximal cough effort. De-
25% of bronchial foreign bodies. In this way, end-inspiratory vices such as cough-assist machines may help to encour-
and end-expiratory films can be helpful in the more coopera- age both an adequate inspiratory and expiratory pressure
tive child. (36) Fluoroscopy and computed tomography (CT) to improve chest clearance, and devices such as chest
have historically been used as alternatives for diagnosis. (36) percussive vests with nebulizer treatments can help to hy-
CT sensitivity approaches 100%, with the only limitation be- drate, break up, and liberate secretions. Assessment of
ing the size of the object. However, if clinically suspected, a mean inspiratory and expiratory pressures can be helpful
foreign body aspiration must be ruled out by bronchoscopy to assess diaphragmatic strength in these patients. (42)
for direct visualization. (36)(37)(38)(39) Auricular Nerve Irritation. Consideration for other, more
Cystic Fibrosis. Cystic fibrosis (CF) is an autosomal re- unusual causes for coughing may stem outside of the air-
cessive genetic disease characterized by 2 disease-causing way, such as in cases of wax or a foreign body in the exter-
mutations in the cystic fibrosis transmembrane conduc- nal ear canal, or in the case of auricular nerve damage
tance regulator (CFTR) gene, which causes the CFTR pro- during neck injury/surgery, or tumor compression. These
tein to become dysfunctional, ultimately resulting in the pathologies irritate the auricular branch of the vagus
mucus of various organs to become thick, tacky, and diffi- nerve, known as the Arnold nerve. Tonsillar size should
cult to mobilize. CF disease has evolved differently with be assessed in these cases, as hypertrophied tonsillar tis-
the advent of extensive genetic testing, newborn screening, sue may impinge on the epiglottis and cause a similar

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 presentation. This is mostly a diagnosis of exclusion. trachea and esophagus. Signs and symptoms similarly in-
Treatment is curative with removal of the foreign body. If clude uncontrolled coughing after swallowing. (46)(47)
nerve irritation is due to nerve damage, treatment with ga- Fungal Pneumonia. Fungal respiratory infection occurs
bapentin has been suggested. (43) either via the inhalation of spores or conidia or by the reacti-
Vascular Rings/Slings. Congenitally abnormal configura- vation of a latent infection. Among fungal infections, asper-
tions/formations of the aortic arch and its major branches gillosis, coccidioidomycosis, and histoplasmosis are the most
can create vascular rings around the trachea and esophagus common. Severe disease mostly affects immunocompro-
with varying degrees of compression. (44) One of the most mised children or children younger than 2 years who may
common anomalies is a double aortic arch, where the as- yet have underdeveloped immune systems. Geographic loca-
cending aorta bifurcates and compresses the trachea and tion has typically been used to stratify risk for a fungal pneu-
esophagus. (44) Signs and symptoms such as harsh-sound- monia, particularly around regions where the ground may
ing cough, stridor, dyspnea, and upper respiratory tract in- be disturbed. As it pertains to US geography, coccidioidomy-
fections present initially in early childhood. Vascular rings cosis is more common in the southwestern regions. Waves
and slings can be diagnosed with the aid of echocardiogra- of infection occur often during earthquakes or near construc-
phy, axial CT, and magnetic resonance imaging. (45) Bron- tion sites. Histoplasmosis is more prevalent in the Missis-
choscopy may be helpful to determine the extent of airway sippi and Ohio River Valley regions, particularly where
narrowing and further guide surgical intervention. Surgery contaminated bat or bird droppings may be a point of con-
is advised for symptomatic patients who have evidence of tact. Blastomycosis is more common east of the Mississippi
tracheal compression. (45) River and has been associated with exposure to ponds and
Tracheoesophageal Fistula. Congenital tracheoesophageal riverbanks. Cryptococcus neoformans is associated with pigeon
fistula (TEF) is a rare condition that occurs in 1 per 3,500 dropping exposure. Aspergillus fumigatus is of particular im-
live births. (46) Clinical presentation depends on the type of portance for the CF airway, or for children with asthma lead-
esophageal atresia. Type C, known by a proximal esophageal ing to a hypersensitivity reaction. Allergic bronchopulmonary
pouch and a distal TEF, accounts for 84% of cases. (46) aspergillosis can be detected via skin testing and serum IgE
TEF occurs without esophageal atresia (H-type fistula) in testing. Cough is typically associated with thick sputum,
only 4%, but it is more common after the neonatal age chest pain, headache, and flulike symptoms. (48)(49)
group. (46) TEF is commonly associated with VACTERL Habit Cough. Terms such as psychogenic cough, tic cough,
(vertebral defects, anal atresia, cardiac defects, TEF, renal vocal cough, and honking cough have all been used to de-
anomalies, and limb abnormalities); Trisomy 13, 21, and 18; scribe habit cough due to its pathognomonic nature. (46)
and congenital heart lesions. (46) Newborns with esophageal Characteristics of this cough include a honking quality,
atresia are unable to swallow saliva or milk, and so gaseous lack of a clear trigger, and absence during distraction or
distention develops via the TEF. (46) Children who present sleep. In cases when the presentation is highly suggestive
with late-onset symptoms such as coughing and cyanosis of this diagnosis, further evaluation is often not necessary.
during feeding, recurrent severe bronchitis, and pneumonia When the presentation is not as clear, diagnosis is by
are more likely to have an H-type fistula. (46) Dry- or wet- exclusion, requiring chest imaging and PFTs to rule out
sounding chronic cough, often barking in character due more indolent causes. Suggestion therapy has been the
to possible concomitant tracheomalacia, recurrent bron- mainstay treatment in children, with the hope that once
chitis and pneumonia, wheezing, and dyspnea are signs the control of cough has been established, the sign may
and symptoms often reported. (46) Cough, tachypnea, completely resolve. Suggestion therapy involves the child
or increased work of breathing are more prominent taking control of their cough and stifling the cough for
around feedings. CT with contrast and flexible fiberoptic longer and longer periods, using slow deep breathing and
bronchoscopy are complementary tools to study airways sips of water to control the urge to cough. This approach
and their relationships with the vascular structures to and a variety of techniques have been reported as being
guide surgical intervention. Bronchiectasis may also de- successful to break the cough-irritation cycle. Other tech-
velop as a consequence of repeated lower respiratory tract niques that have been described include self-hypnosis,
infections. (46)(47) speech therapy, and behavioral interventions. (50)(51)
Acquired TEF is likewise a rare entity and occurs as a Mediastinal Masses. Mediastinal masses may suggest their
result of trauma, radiotherapy secondary to malignancy, etiology by their location. These masses may be located in the
granulomatous infection, and previous surgery of the anterior, middle, or posterior mediastinum. Many of these

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 masses are asymptomatic and have more indolent courses. dabbing or dripping, smoking concentrated tetrahydrocan-
Anterior mediastinal masses, which may be lymphoma, tera- nabinol or nicotine prepared in wax and smoked in a pipe,
toma, or thymoma, can present with coughing or dyspnea or inhaling the vapor produced from placing concentrated
when the child is supine. The anterior mediastinal location butane hash oil or nicotine on a hot surface have also be-
yields masses with the most signs and symptoms and are come popular.
more readily diagnosed. Middle mediastinal masses may com- Ninety-five percent of patients present with respiratory
press blood flow via obstruction of the superior vena cava and symptoms of cough, chest pain, and shortness of breath,
sometimes cause airway obstruction. Most often these masses which progress in severity over 1 to 2 weeks. Auscultation is of-
are incidental findings and include bronchogenic cysts, cardiac ten normal. Nonspecific findings such as leukocytosis, elevated
tumors, cystic hygromas, or vascular abnormalities. Posterior erythrocyte sedimentation rate, and elevated liver enzyme levels
mediastinal masses are rarer yet and include esophageal du- have been reported. The chest radiograph is abnormal in most
plication, meningomyelocele, neuroenteric abnormalities, or cases, revealing bilateral patchy/diffuse infiltrates. Chest CT
neurogenic tumors. Chest radiography and, ultimately, CT of commonly exhibits predominantly bibasilar consolidations and
the chest or magnetic resonance imaging can help make the diffuse ground-glass opacities. Treatment with antibiotics tar-
diagnosis. A biopsy is usually needed to confirm and create a geted toward severe community-acquired pneumonia are rec-
treatment plan. (52) ommended at the time of presentation. Oral or intravenous
corticosteroids can be used. The long-term consequences of
Emerging Causes of Chronic Cough electronic cigarette/vape–related acute lung injury are un-
Coronavirus Disease 2019 Related. The novel severe acute known, and so pulmonary function tests, 6-minute walk with
respiratory syndrome coronavirus 2 has proved itself to be a pulse oximetry, and CT of the chest may be considered 1 to
multifaceted pathogen, and although most confirmed pediat- 2 months after presentation, and followed over time. (54)
ric cases present asymptomatically or with mild upper respi-
ratory tract symptoms, there is evidence that a small CLINICAL CASE FOLLOW-UP
percentage of cases can progress to acute respiratory distress In the previously mentioned case, follow-up chest radiog-
syndrome or multiorgan system dysfunction. The most com- raphy and subsequent CT of the chest revealed a large me-
mon coronavirus disease 2019 (COVID-19) illness signs and diastinal mass with a midline shift. The neck swelling and
symptoms include fever, fatigue, shortness of breath, joint cough were considered to be secondary to lymphatic ob-
pain, chest pain, cough, and loss of taste or smell. Reports of struction by the mass, which proved to be a non-Hodgkin
chronic cough after COVID-19 illness are not yet definitively lymphoma confirmed by biopsy. After chemotherapy and
established. Overall, chronic cough has been evident in only radiotherapy, the child continues to do well.
24.7% of young children (7–10 years) vs 26% of older chil-
dren (12–17 years). (53) CONCLUSION
Electronic Cigarette/Vape–Related Acute Lung Injury. Cough is a normal protective mechanism of the airway. Pro-
Electronic cigarettes are battery-powered, often handheld longed cough most commonly presents after a viral upper
devices that heat a liquid that contains nicotine, flavorings, respiratory tract infection. Postinfectious hypersensitivity is
and other chemicals to produce an aerosol, which is then considered an important etiological factor in the persistence
inhaled. The exhaled smoke has been perceived to be water of cough. Many common causes of cough have specific
vapor, when it is in fact a collection of fine particles. The e- “cough pointers”—types of cough or associations—that can
liquid used in these devices are usually propylene glycol or provide clues to diagnoses. Although the respiratory system
a vegetable glycerin-based substance with nicotine, a gamut is the most commonly affected in cases of persistent cough,
of flavorings, and often other chemicals and metals. One extrapulmonary causes must be carefully considered in spe-
electronic cigarette most often used by adolescents uses a cific situations. In addition to asthma, common causes of
compact device that resembles a USB flash drive and deliv- prolonged cough include PBB, chronic GER, and UACS. In
ers high doses of nicotine equivalent to 20 cigarettes per cases when signs and symptoms persist, it may be worth-
pod. Tetrahydrocannabinol can be added to electronic ciga- while for the pediatrician to consider uncommon causes of
rettes alone or in conjunction with nicotine. Unfortu- chronic cough, such as retained foreign body, CF, and
nately, the market has encouraged illicit dealers to create structural anomalies. Emerging causes such as electronic
potentially toxic combinations of substances that often cigarette/vape–related acute lung injury and COVID-19–re-
contain vitamin E and cannabinoid oils. Processes such as lated cough are still being fully investigated. A clear

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 understanding of the pathophysiology and etiology of com-
• According to grade 2 evidence, antihistamines
mon causes of cough, a detailed history, careful physical ex-
and intranasal corticosteroids are helpful for
amination, and judicious investigations can most often lead
allergic cough.
the pediatrician to the right diagnosis and management.
• According to grade 1 evidence, over-the-counter
Summary cough suppressants are comparable to placebo and
may have potential for adverse effects. According to
• According to grade 1 evidence, cough can be
grade 1 evidence, for children 14 years and younger
normal, but it is important to consider clues in
with chronic cough without an underlying lung
either history or examination that can point to
disease, treatment for gastroesophageal reflux
treatable causes. In most patients, cough is related
disease should not be used when there are no
to viral upper respiratory tract infection, and
clinical features of gastroesophageal reflux.
supportive measures alone will be sufficient.
According to grade 2 evidence, bronchodilators are
• According to grade 1 evidence, chest imaging should not effective and should be avoided in nonasthmatic
be obtained in the presence of nontraditional history children.
or cough characteristics, lower respiratory tract
• According to grade 1 evidence, children should be
symptoms, relentless progressive coughing, or
removed from environmental tobacco smoke or
hemoptysis.
pollutant exposure.
• According to grade 1 evidence, children with a
history of cough with suspicion of foreign body
should undergo urgent bronchoscopy.
References and teaching slides for this article can be found at
https://doi.org/10.1542/pir.2021-005398.

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 PIR QUIZ

1. A 7-year-old girl with asthma returns to the clinic after yearly evaluation with her
pulmonologist who manages her inhaled corticosteroid. She continues to have
exacerbations and cough in the late summer during harvesting season. The
patient’s mother states that the pulmonologist completed pulmonary function
testing but in addition completed fractional exhaled nitric oxide testing to
evaluate the treatment efficacy of which of the following conditions?
A. Allergic asthma.
B. Gastroesophageal reflux disease.
C. Habit cough.
D. Postinfectious hypersensitivity. REQUIREMENTS: Learners can
E. Protracted bacterial bronchitis. take Pediatrics in Review quizzes
and claim credit online only at:
2. A 5-year-old boy is evaluated in the clinic for cough of 4 weeks’ duration. When http://pedsinreview.org.
the cough began 4 weeks ago, it was associated with congestion, fever, and
fatigue. These associated symptoms resolved over the following 7 days, but the To successfully complete 2022
Pediatrics in Review articles for
cough remained persistent. The child has no history of wheezing, allergies, or
AMA PRA Category 1 Credit™,
prolonged respiratory symptoms. There is no secondhand smoke exposure. On learners must demonstrate a
physical examination vital signs are all within normal limits, and lungs are clear to minimum performance level of
auscultation with no focal crackles or wheezes. Which of the following is the most 60% or higher on this
appropriate pharmacotherapy for the cough? assessment. If you score less
than 60% on the assessment,
A. Albuterol. you will be given additional
B. Amoxicillin. opportunities to answer
C. Clindamycin. questions until an overall 60%
D. Corticosteroids. or greater score is achieved.
E. Ipratropium.
This journal-based CME activity
3. A previously healthy, fully vaccinated 2-year-old is evaluated for the fourth time for is available through Dec. 31,
cough in the past 6 weeks. He is afebrile and in no respiratory distress. He has 2024, however, credit will be
recorded in the year in which
mildly decreased lung sounds in the right lower lobe with no crackles or wheezing.
the learner completes the quiz.
He has completed 2 courses of appropriate antibiotics for community-acquired
pneumonia. Albuterol does not seem to improve his cough. Evaluation so far has
been limited to viral testing, which is negative. Which of the following chest
imaging studies is the most appropriate next step in management?
A. Computed tomography.
B. Magnetic resonance imaging. 2022 Pediatrics in Review is
C. Radiography. approved for a total of 30
D. Positron emission tomography. Maintenance of Certification
(MOC) Part 2 credits by the
E. Ultrasonography. American Board of Pediatrics
4. A 10-year-old girl is evaluated for cough during the past 8 weeks. The parents (ABP) through the AAP MOC
Portfolio Program. Pediatrics in
describe it as a nonproductive cough that sounds like a “honking noise.” It is most
Review subscribers can claim up
prevalent when she is resting such as watching television. They do not hear her to 30 ABP MOC Part 2 points
cough at night. She has had no associated symptoms such as congestion, fever, upon passing 30 quizzes (and
weight loss, or fatigue. Which of the following is the best next step in management? claiming full credit for each
quiz) per year. Subscribers can
A. Albuterol as needed.
start claiming MOC credits as
B. Amoxicillin. early as October 2022. To learn
C. Bronchoscopy. how to claim MOC points, go
D. Chest radiography. to: https://publications.aap.org/
E. Suggestion therapy. journals/pages/moc-credit.

702 Pediatrics in Review

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 5. A 16-year-old is evaluated for cough with associated chest pain during the
past 2 weeks. The cough has slowly worsened and it is now difficult to
complete daily tasks due to shortness of breath. Lung examination reveals
no crackles or wheezing. The patient is afebrile. He denies smoking tobacco
but admits to vaping and using e-cigarettes. Laboratory evaluation including
a complete blood cell count and complete metabolic panel is significant for
elevated white blood cell count and aspartate aminotransferase level. Chest
radiography is ordered. The chest radiograph is most likely to show which of
the following findings?
A. Bilateral diffuse infiltrates.
B. Enlarged cardiac silhouette.
C. Large pleural effusion.
D. Lobar consolidation.
E. Pneumothorax.

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