Paediatric Chronic Cough: Defining illness burden and causes

Chronic cough is a common problem of various etiologies. While diagnosis may relatively be easy in the presence of some specific findings, it tends to be rather difficult when there are no clear symptoms. Therefore, practical guidelines are needed for management of patients with chronic cough. We aimed to evaluate assessment and management of chronic cough in children according to the British Thoracic Society guidelines published in 2008. Patients with chronic cough lasting longer than 8 weeks between 5 and 16 years old were evaluated. Pulmonary function test and chest radiography were performed on all patients. Further workup was conducted on those requiring further investigation. Patients were re-evaluated at 2- to 4-week intervals, and we followed our patients for 18 months until cough resolved. One hundred fifty six patients (52.5% female) aged 5-16 (8.42 ± 2.6) years were included. Of the 156 patients, 19.2% (n = 30) were diagnosed with postnasal drip syndrome plus asthma; 18.6% (n = 29) with postnasal drip syndrome; 12.2% (n = 19) with asthma; 12.2% (n = 19) with protracted bacterial bronchitis; and 11.5% (n = 18) with nonspecific isolated cough, 9.6% (n = 15) with cough variant asthma, 5.7% (n = 9) with psychogenic cough and 3.2% (n = 5) with gastroesophageal reflux disease. Postnasal drip syndrome and asthma was the most common cause of chronic cough. Asthma-associated findings were found in some of the patients diagnosed with postnasal drip syndrome. It has been observed that there could be more than one particular cause for cough concerning some patients. The gastroesophageal reflux disease was not a common primary cause of chronic cough in children.

Background/Aims: Chronic cough is a prevalent issue in pediatric patients and is among the most common reasons for referral to pediatric allergists, significantly affecting quality of life and often necessitating specialized evaluation. This study aimed to analyze the clinical characteristics, etiologies, and management of chronic cough in children, providing insights into age-related prevalence. Methods: Pediatric patients presenting with chronic cough to our pediatric allergy clinic between May 1,2023 and May 31, 2024 were included in this retrospective study. Patients previously diagnosed with allergic diseases or evaluated at other clinics were excluded. Medical records were reviewed for demographics, cough characteristics, familial and environmental factors, and treatments. Results: Of the 267 patients included, 54.7% were boys, and the median age was 6.99 (interquartile range (IQR) 4.47-11.54) years. Asthma (39%), protracted bacterial bronchitis (PBB) (25.8%), and upper airway cough syndrome (UACS) (22.1%) were the most common diagnoses. PBB was more prevalent in younger patients, whereas asthma was dominant in older age groups. Regardless of the cough etiology, antibiotic use was noted in 67.8% of patients before applying to the pediatric allergy outpatient clinic. Tobacco smoke exposure was present in 40.1% of patients. Familial asthma history was significantly more common in patients with asthma (p=0.04). Conclusions: This study underscores the importance of distinguishing chronic cough etiologies in children to prevent mismanagement and overuse of antibiotics. While asthma, PBB, and UACS were among the primary causes, many other potential diagnoses also warrant consideration. Comprehensive assessments are essential for accurate diagnosis, and a multi-disciplinary approach may enhance management outcomes.

Cough is a natural process that protects the airway. Cough can occur spontaneously or voluntarily. It is considered chronic when it is present for longer than 4 weeks in children or 8 weeks in adults. In both, chronic cough causes patient distress and increased healthcare utilization. Etiologies of pediatric chronic cough include asthma, protracted bacterial bronchitis, tracheomalacia, habit cough, and various systemic disorders. While some diagnoses are identifiable by careful history alone, others require testing guided by specific pointers. Flexible fiberoptic bronchoscopy has been an important tool to identify etiologies of chronic cough that were not otherwise apparent. In adults, asthma and bronchitis are well-defined etiologies of chronic cough, but much chronic cough in adults is largely a conundrum. Reviews of adult chronic cough report that at least 40% of adults with chronic cough have no medical explanation. Gastroesophageal reflux and upper airway cough syndrome (a.k.a. post-nasal drip) have been common diagnoses of chronic cough, but those diagnoses have no support from controlled clinical trials and have been subjected to multiple published critiques. Cough hypersensitivity is considered to be an explanation for chronic cough in adults who have no other confirmed diagnosis. Gabapentin, a neuromodulator, has been associated with a modest effect in adults, as has speech pathology. While habit cough has not generally been a diagnosis in adults, there is evidence for a behavioral component in adults with chronic cough. Treatment for a specific diagnosis provides a better outcome than trials of cough suppression in the absence of a specific diagnosis. More data are needed for chronic cough in adults to examine the hypothesized cough hypersensitivity and behavioral management. This article reviews etiologies and the treatment of chronic cough in children and the conundrum of diagnosing and treating chronic cough in adults.

A cough that lasts for more than 8 weeks in adults (those older than 15 years) and more than 4 weeks in children is considered chronic and poses a significant health problem, as it can lead to feelings of fatigue, sleep disturbances, hoarseness, disruption of daily activities, vomiting, and often in women, even incontinence. The differential diagnosis of chronic cough in adults and children has its specificities. In certain cases, the etiological factor remains unknown when referring to unexplained (idiopathic) chronic cough. This paper presents the results of a systematic review of publications in medical databases (PubMed) and guidelines from the European Respiratory Society (ERS) and the American College of Chest Physicians (CHEST), related to the diagnosis and treatment of chronic cough. Diagnostic investigations should be focused on the most common causes of chronic cough. In adults, these include asthma, chronic obstructive pulmonary disease, bronchiectasis, interstitial lung disease, lung malignancy, non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airway cough syndrome. In children, the most common causes of chronic cough are asthma, protracted bacterial bronchitis, cystic fibrosis, primary ciliary dyskinesia, bronchiectasis, tracheobronchomalacia, pertussis, habitual (psychogenic) cough, and foreign body aspiration. The treatment primarily involves excluding medications that might have chronic cough as an adverse effect. Therapy is directed toward treating the underlying cause of chronic cough. If the cough persists despite treatment (refractory cough) or if it's idiopathic, neuromodulatory medications are employed (opioids, gamma-aminobutyric acid analogs, tricyclic antidepressants). Therapeutic options also include breathing and vocal techniques, superior laryngeal nerve blocks, and vocal cord medialization injections. Drugs directly inhibiting sensory receptors (P2X3, TRPV-1, and NK-1 inhibitors) are currently under clinical trial investigation. The use of validated tests is crucial for assessing therapeutic effectiveness. The etiological factors of chronic cough can have both infectious and non-infectious origins and are not always related to lung diseases. Considering that chronic cough is regarded as a condition of hypersensitivity, when causal treatment does not yield satisfactory results or when dealing with idiopathic chronic cough, therapy is directed towards central or peripheral neuromodulation, as well as techniques involving breathing and vocal production.

Chronic respiratory disease is common among Aboriginal Australians. Chronic wet cough is an early marker of chronic disease in children but often goes undetected due, in part, to delayed health seeking by families. Currently, no studies have examined the reasons for delayed health seeking for children's chronic cough. To identify the barriers to, and enablers for, seeking medical help for chronic wet cough in Aboriginal children. This was a qualitative study, gathering data through individual semi-structured, in-depth interviews and focus groups to ascertain Aboriginal family knowledge, attitudes and beliefs about seeking health care for chronic wet cough in children in a regional Kimberley town, Western Australia between October 2017 and March 2018. Forty Aboriginal community members participated. The three key barriers identified were: 'Cough normalisation', that is, 70% of participants considered chronic cough normal (with 53% of participants' previous interactions with doctors informing their understanding of chronic cough); the lack of health literacy information; and a sense of disempowerment (belief that no medical action would be taken and inability to challenge doctors). The key expressed enablers were provision of health literacy information and health practitioner training to assess and treat chronic wet cough in children. All participants reported that they would seek help for chronic wet cough once they were informed that it could signify underlying disease. Results highlight the need for a culturally appropriate information and education to inform Aboriginal families and their health practitioners of the importance of chronic wet cough in children.

Cough as a symptom is one of the most common reasons for acute presentations to doctors. The burden of illness (number of presentations to doctors, impaired quality of life, and stress to parents) associated with chronic cough (>4 wk duration) in children is high and is independent of the etiology. When the chronic cough resolves, the level of stress and quality of life scores significantly improve to population norms. Moreover, chronic cough can be a symptom of an underlying serious disease such as aspiration lung disease or bronchiectasis. Thus, all children with cough require a systematic evaluation and approach. This approach, which is different from adults, is briefly outlined in this review. Physiological reasons why chronic cough in children is different from adults includes the domains that relate to (i) cough-specific physiology, (ii) general respiratory physiology, (iii) other direct systems such as the immune system that influence the respiratory system, and (iv) other general physiology. Several conditions associated with chronic cough in children have further been studied recently. These conditions that include protracted bacterial bronchitis, obstructive sleep apnea, tracheomalacia, and exercise-associated cough are also discussed in this review.

Cough is one of the most common symptoms the children experience at the preschool age, and in most cases, cough associated with viral respiratory infection improves within 2-4 weeks. In preschool-aged children, prolonged cough is usually wet or productive due to mucus secretion. Although prolonged cough no doubt has an influence on the quality-of-life of both the children and families,1 the epidemiology of prolonged or wet cough is poorly known. Sørensen et al2 published in this issue of the journal their interesting findings on recurrent episodic or chronic wet cough in Norwegian preschool-aged children, with a special focus paid on presence of symptoms 5-7 years later. The study subjects were collected retrospectively from electronic files of an academic hospital and comprised patients admitted for chronic or prolonged respiratory symptoms like cough to the outpatient clinic during three years in 2010-2013 at younger than 3 years of age. The design was population-based in that sense that the study subjects, though representing severe cases, lived in a geographically defined area. In 2017-2018, questionnaires were sent to the parents of 840 identified patients, and 348 answered, and 291 cases were accepted for the final analyses.2 These cases were divided after retrospective chart review into two groups, those 171 with recurrent episodic and those 120 with chronic wet cough. The annual age-specific prevalence of recurrent episodic or chronic wet cough, estimated from these figures, was around 1.5% in younger than 3-year-old children. Children with chronic wet cough were younger, and their symptoms deputed earlier compared to those with recurrent episodic wet cough.2 The median age at onset of wet cough was six vs 10 months and on admission 16 vs 22 months, respectively. These figures fit well with those in the available literature.3-5 The symptoms had continued for 8-9 months before admission, which is a long time at this young age of less than 2 years on average. No doubt, such symptomatic time of more than half year decreases the quality-of-life in children and increases mental, social and economic burdens to the families.1 Antibiotics were prescribed to 21.6% of the children during 6 months before or at the first visit, the figure being higher, but only 33.3%, in those with chronic wet cough, compared to 13.3% in those with recurrent episodic wet cough.2 These observations may reflect an avoidance of antibiotic prescription to diminish side effects in children and to restrain emergence of antibiotic resistance, which, of course, are important aspects to be taken into account especially in preschool-aged children.6 Instead, asthma medicines were often used, the figures being 60.8% for beta2-agonists and 47.6% for inhaled corticosteroids (ICSs) during the last 6 months before admission, without any substantial differences between the groups.2 The authors summarised that half of the children continued or were prescribed ICSs at the primary visit, although cough without wheezing should not be considered as asthma.2 A substantial proportion of included children were examined by young residents and not by paediatric pulmonologists or other specialists, which may have decreased the adherence to asthma guidelines.2 Obviously, the situation is similar in most teaching hospitals in different countries. At the follow-up at the median age of 6.8 years, over half of the study subjects reported of being without marked symptoms during the last year.2 However, 36.9% of children in the recurrent episodic and 23.5% in the chronic wet cough group had still received beta2-agonists during the last 6 months. The respective figures were 27.2% and 18.6% for the use of inhaled ICSs.2 The figures are rather high, but the design of the study did not allow to evaluate whether there was any over-use of asthma medications. The majority of preschool-aged children with recurrent episodic or chronic wet cough have protracted bacterial bronchitis (PBB), which is a distinct clinical entity defined by the presence of wet or productive cough for at least 4 weeks without evidence of an underlying illness.3, 4 Tracheo- and/or bronchomalacia and gastro-oesophageal reflux are common in young children with PBB5 and do not belong to the exclusion criteria.3 In the currently available guidelines, children with PBB should be treated with rather long antibiotic courses of 2-4 weeks.3, 4 Research-based evidence beyond this recommendation is scarce. Only three randomised controlled trials with varying treatment times have been published on antibiotics in children with wet cough.7 Understandable, many doctors are worried that such courses may lead to unnecessary consumption of antibiotics with known harmful effects. Current concepts on the occurrence, risk factors and outcomes of recurrent and chronic wet or productive cough are based on conclusions of expert panels set by medical societies.3, 4 Before the study of Sørensen et al,2 only short follow-ups of small patient groups were available.8, 9 In addition, clinical experience and the few available studies on PBB come from Australia and some Asian countries, such as China and Turkey.9 Probably, genetic susceptibilities to certain chronic pulmonary diseases, such as bronchiectasis with or without cystic fibrosis, differ between different populations. A whole-population study was done in 2017-2018 among Australian under 7 years old aboriginals, and the prevalence of chronic wet cough was as high as 13%.10 This is the only strictly population-based study made thus far on prolonged or chronic wet cough. The study of Sørensen et al2 is an important start for studies on recurrent or chronic wet cough in European children. The study was retrospective and hospital-based. The next step should be performance of population-based studies with both retrospective and prospective designs covering the whole spectrum of the disease. The treatment with antibiotics for 2-4 weeks has been effective in the selected group of children with PBB, but the challenges for the clinicians are how to recognise those children likely to benefit from treatment and how extensive differential diagnostics is needed before treatment. The author has no conflicts of interest to declare. Matti Korppi

Etiological factors of chronic cough in children: Don’t ignore obstructive sleep apnea

To assess the use of a standardized evaluation algorithm [American College of Chest Physician (ACCP) 2006] in children with chronic cough. In this prospective cohort study, children with chronic cough were evaluated as per the ACCP 2006 diagnostic algorithm. All children were followed regularly at an interval of 2-4 wk. The study's endpoint was for the patient being cough free for four weeks either following treatment or naturally. The mean age of the 87 studied children (52 male, 35 female) was 11.9±3 y. Forty children (45.9%) had specific cough pointers on history and examination. Radiograph showed abnormalities in 12 (13.8%) children, and spirometry showed a reversible obstructive pattern on spirometry in 6 (6.9%) among 47 (54%) children without specific cough pointers. After a detailed evaluation, 16 (18.3%) children had no remarkable findings and were reviewed after two weeks. Spontaneous resolution of cough occurred in 6 children. A trial of inhalational corticosteroids (ICS) (9 children) or antibiotics (1 child) was given to the rest of the ten children. Specific underlying diagnoses could be established in 80 (91.9%) children. The most common etiology identified in the study was asthma and asthma-like illnesses (n = 52; 59.8%), followed by upper airway cough syndrome (n=13; 14.9%) and tuberculosis (n = 9; 10.4%). Eighty-four (96.5%) children had complete resolution of cough during follow-up. The mean time to resolution in the study was 33.6±16.8 d. This study demonstrated that the ACCP 2006 algorithm is effective in establishing the underlying etiology and managing children with chronic cough.

Protracted bacterial bronchitis: The last decade and the road ahead.

Pro: Children with chronic cough present a diagnostic challenge. Protracted bacterial bronchitis (PBB) is a chronic, persistent bacterial infection of conducting airways defined by the presence of cough for longer than 4 weeks that resolves with antimicrobial therapy and without an alternative diagnosis. The diagnosis is made by the findings of increased bronchial secretions and edema of the lower airways on flexible bronchoscopy and positive cultures on bronchoalveolar lavage. It is speculated that an initial respiratory insult such as viral infection disrupts normal surface morphology and ciliary function, which leads to chronic self-perpetuating inflammation with the formation of bacterial biofilms, leading to PBB. PBB is often misdiagnosed as asthma, leading to inappropriate and excessive use of steroids. The importance of timely diagnosis should be emphasized due to the potential that PBB may be a precursor to chronic suppurative lung disease or bronchiectasis if left untreated; however, every patient should be adequately assessed to exclude other causes of chronic cough. Con: Clinical criteria for the diagnosis of PBB are nonspecific and may not distinguish it from other known causes of chronic cough, including viral infections. Benefits from antibiotic therapy (particularly prolonged therapy) have not been demonstrated. Respiratory conditions are the most common reason for antibiotic prescriptions during ambulatory visits in the United States, and many of these prescriptions are inappropriate and/or unnecessary. The proposed diagnostic criteria and recommendations for the treatment of PBB will lead to unnecessary overuse of antibiotics.

Chronic cough (a cough lasting longer than 4 weeks) is a common symptom presenting to primary care in Australia and internationally. Chronic cough costs the community, is distressing to parents, and ignoring cough may lead to delayed diagnosis and illness progression of serious underlying respiratory disease. Clinical guidelines have been shown to provide more efficient and effective patient care and can clarify clinical decision making. Cough guidelines have been designed to facilitate management of chronic cough, however treatment recommendations vary and specific clinical pathways for the treatment of chronic cough in children are important, as the cause and treatments for cough in a child vary significantly adults. Therefore, it would be beneficial to clinical practice to systematically evaluate the use of clinical pathways for the treatment of chronic cough in children. To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. The Cochrane Register of controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The search was carried out in May 2007. All randomised controlled trials with parallel group design comparing use vs non-use of a clinical pathway for treatment of chronic cough in children. Results of searches were reviewed against the pre-determined criteria for inclusion. Two reviewers independently selected the studies and it was planned that data extraction would have been done in duplicate. The search identified 471 potentially relevant titles but no studies met criteria for inclusion in the review. Without further available evidence, recommendations for the use of clinical pathways for the treatment of chronic cough in children cannot be made. Until further evidence is available, the decision for further investigation and treatment for the child presenting with chronic cough should be made on an individual basis (i.e. dependent on symptoms and signs) with consideration for existing data from other Cochrane reviews on specific treatments for cough. Trials are required to provide evidence on the effectiveness of clinical pathways for the treatment of chronic cough in children.

What Is the Burden of Chronic Cough for Families?

Cough (lat.tussis) is an automatic, natural reflex (without human will) that helps expel secretions, various irritants, foreign particles and microorganisms from the airways.In children, the most common cause of cough is the accumulation of secretions in the respiratory tract as a result of an allergy or infection.According to the duration, cough can be divided into: acute cough that lasts up to 4 weeks and chronic cough that lasts longer than 4 weeks.Most cases of acute cough in children are associated with viral infections of upper respiratory tract and do not require specific diagnostic evaluation.Treatment of upper respiratory tract infections (URTIs) requires antipyretics, good hydration and aspiration of secretions.Intranasal steroids may be effective in children with allergic rhinitis that presents with cough during the pollen season.The causes of chronic cough in children vary depending on the age of the patient.The most common cause of non-specific chronic cough in children under 5 years of age is as a result of upper respiratory tract infection (37.6%), followed by asthma-like cough (31.8%) and post-infectious cough (18.8%).Chronic cough due to asthma requires treatment with bronchodilators and, depending on the classification, inhaled corticosteroids.In the case of allergic rhinitis, antihistamines and topical corticosteroids will be needed, at least for a month.The use of antihistamines has been shown to be very effective in patients with allergic cough.And that in groups of children with allergic asthma, allergic rhinitis and asthma, allergic rhinitis without asthma and atopic cough Treatment of allergic cough usually lasts about six months.

Chronic cough in preschool children