Protracted Bacterial Bronchitis Research Articles

Diagnostic Support for Selected Paediatric Pulmonary Diseases Using Answer-Pattern Recognition in Questionnaires Based on Combined Data Mining Applications--A Monocentric Observational Pilot Study.

BackgroundClinical symptoms in children with pulmonary diseases are frequently non-specific. Rare diseases such as primary ciliary dyskinesia (PCD), cystic fibrosis (CF) or protracted bacterial bronchitis (PBB) can be easily missed at the general practitioner (GP).ObjectiveTo develop and test a questionnaire-based and data mining-supported tool providing diagnostic support for selected pulmonary diseases.MethodsFirst, interviews with parents of affected children were conducted and analysed. These parental observations during the pre-diagnostic time formed the basis for a new questionnaire addressing the parents’ view on the disease. Secondly, parents with a sick child (e.g. PCD, PBB) answered the questionnaire and a data base was set up. Finally, a computer program consisting of eight different classifiers (support vector machine (SVM), artificial neural network (ANN), fuzzy rule-based, random forest, logistic regression, linear discriminant analysis, naive Bayes and nearest neighbour) and an ensemble classifier was developed and trained to categorise any given new questionnaire and suggest a diagnosis. For estimating the diagnostic accuracy, we applied ten-fold stratified cross validation.ResultsAll questionnaires of patients suffering from CF, asthma (AS), PCD, acute bronchitis (AB) and the healthy control group were correctly diagnosed by the fusion algorithm. For the pneumonia (PM) group 19/21 (90.5%) and for the PBB group 17/18 (94.4%) correct diagnoses could be reached. The program detected the correct diagnoses with an overall sensitivity of 98.8%. Receiver operating characteristics (ROC) analyses confirmed the accuracy of this diagnostic tool. Case studies highlighted the applicability of the tool in the daily work of a GP.ConclusionFor children with symptoms of pulmonary diseases a questionnaire-based diagnostic support tool using data mining techniques exhibited good results in arriving at diagnostic suggestions. In the hands of a doctor, this tool could be of value in arousing awareness for rare pulmonary diseases such as PCD or CF.

Pro-Con Debate: Protracted Bacterial Bronchitis as a Cause of Chronic Cough in Children.

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.

Recognition and management of children with protracted bacterial bronchitis.

Chronic moist cough in children can be associated with serious pathologies. Protracted bacterial bronchitis remains a clinical diagnosis causing persistent moist cough, disturbed sleep, exercise intolerance and significant levels of morbidity. Management involves minimal investigations and prolonged courses of antibiotics.

Recurrent, protracted and persistent lower respiratory tract infection: A neglected clinical entity

Community-acquired pneumonia is a potentially life-threatening disease affecting children worldwide. Recurrent pneumonia episodes can lead to the development of chronic respiratory morbidity. Chronic wet cough, a common pediatric complaint, is defined as a wet cough indicating excessive airway mucus that lasts for a minimum of 4 weeks. Most children with a chronic wet cough do not suffer from underlying debilitating pulmonary disorders. Rather, chronic wet cough is generally associated with neutrophilic airway inflammation and bacterial infections of the conducting airways. Failure to characterize endobronchial infections has led to under-recognition of chronic wet cough as an important clinical entity in children. Under-recognition and under-treatment of protracted bacterial bronchitis (PBB), a diagnosis made by the presence of isolated cough >4 weeks that resolves with appropriate antibiotic treatment, may lead to the development of chronic suppurative lung disease (CSLD) and bronchiectasis. The burden of bronchiectasis is highest in developing countries and in specifically vulnerable populations in developed countries, in particular indigenous children living in remote communities. The incidence, hospitalization rates and risk of long term sequelae of childhood pneumonia in indigenous children are higher than in non-indigenous children residing in the same area. The overlapping clinical and pathophysiological characteristics of PBB, CSLD and bronchiectasis are the presence of a chronic wet cough, impaired mucociliary clearance of the conducting airways, the presence of endobronchial bacterial infection (mainly non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis) and neutrophilic airway inflammation. The principles of managing PBB, CSLD and bronchiectasis are the same. More research and public health interventions are required to improve the awareness, diagnosis and management of these causes of chronic wet cough in children.

Toux traînantes chez l’enfant et l’adolescent

A persistent cough lasting more than 4–8weeks should lead to a diagnostic workup. A detailed history and a full clinical examination, with a chest X-ray, are essential for initial assessment. Most reported causes of chronic cough in children are post-nasal drip syndrome, cough variant asthma (a spirometry with test of bronchodilator responsiveness should be attempted in children old enough to perform the manoeuvres). GERD is often suspected but a causal relationship is difficult to establish. Protracted bacterial bronchitis, post-infectious cough (B. pertussis, Mycoplasma) and somatoform respiratory disorders (including hyperventilation syndrome) are also common. Signs which are pointers suggesting an underlying respiratory or systemic disease require further investigation: inhaled foreign bodies, cystic fibrosis and chronic lung diseases with bronchiectasis, airway abnormalities, interstitial lung diseases need to be considered. Recent reports of refractory coughs have identified features of a sensory neuropathy disorder, and might explain persistent cough triggers.

Mediators of Neutrophil Function in Children With Protracted Bacterial Bronchitis

Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB. BAL was collected from children in an experimental cohort (n = 21, PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n = 11, control subjects). IL-1β, IL-1 receptor antagonist (IL-1RA), and α-defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules. In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1β and α-defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated. PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.

PO-0012 Managing Children With Protracted Bacterial Bronchitis

Introduction It is important that health professionals consider a list of differential diagnoses when faced with a child with chronic cough (acute cough usually lasts less than three weeks). Potential causes include: asthma, cystic fibrosis, foreign body aspiration, anatomical abnormalities of the airways and other disorders. Studies have shown that children with chronic wet cough often have bronchitis and this is evident on bronchoscopy. Protracted bacterial bronchitis (PBB) is defined as persistence of isolated wet cough lasting more than four weeks and responding to antibiotic treatment. Diagnosis Clinical is achieved by presence of wet cough lasting >4 weeks. It is primarily a neutrophilic disease and presence of respiratory bacterial pathogens has been demonstrated in bronchoalveolar lavage. Prolonged course of oral antibiotics of 2–3 weeks is suggested as the initial therapy. Treatment is likely to result in symptom resolution and may minimise the risk of developing bronchiectasis. Chest X-ray may be performed in some cases and will be found to be normal in most instances. Sputum culture may also be sent in older children. Diagnosis may be confirmed by bronchoscopy with BAL followed by bacterial study; however, such an invasive approach may not be deemed necessary or may not be readily available in most cases. Treatment The British Thoracic Society (BTS) advises using four to six weeks of oral antibiotics.4 In the absence of a bacterial culture a prolonged course of either amoxicillin or a macrolide antibiotic is suggested in most children with PBB.

Bacterial Distribution in the Lungs of Children with Protracted Bacterial Bronchitis

ObjectivesFlexible bronchoscopy with bronchoalveolar lavage (FB-BAL) is increasingly used for the microbiological confirmation of protracted bacterial bronchitis (PBB) in children with a chronic wet cough. At our centre, when performing FB-BAL for microbiological diagnosis we sample 6 lobes (including lingula) as this is known to increase the rate of culture positive procedures in children with cystic fibrosis. We investigated if this is also the case in children with PBB.MethodsWe undertook a retrospective case note review of 50 children investigated for suspected PBB between May 2011 and November 2013.ResultsThe median (IQR) age at bronchoscopy was 2.9 (1.7–4.4) years and the median (IQR) duration of cough was 11 (8.0–14) months. Positive cultures were obtained from 41/50 (82%) and 16 (39%) of these patients isolated ≥2 organisms. The commonest organisms isolated were Haemophilus influenzae (25 patients), Moraxella catarrhalis (14 patients), Staphylococcus aureus (11 patients) and Streptococcus pneumoniae (8 patients). If only one lobe had been sampled (as per the European Respiratory Society guidance) 17 different organisms would have been missed in 15 patients, 8 of whom would have had no organism cultured at all. The FB-BAL culture results led to an antibiotic other than co-amoxiclav being prescribed in 17/41 (41%) patients.ConclusionsBacterial distribution in the lungs of children with PBB is heterogeneous and organisms may therefore be missed if only one lobe is sampled at FB-BAL. Positive FB-BAL results are useful in children with PBB and can influence treatment.

Three Clinically Distinct Chronic Pediatric Airway Infections Share a Common Core Microbiota

DNA-based microbiological studies are moving beyond studying healthy human microbiota to investigate diverse infectious diseases, including chronic respiratory infections, such as those in the airways of people with cystic fibrosis (CF) and non-CF bronchiectasis. The species identified in the respiratory secretion microbiota from such patients can be classified into those that are common and abundant among similar subjects (core) versus those that are infrequent and rare (satellite). This categorization provides a vital foundation for investigating disease pathogenesis and improving therapy. However, whether the core microbiota of people with different respiratory diseases, which are traditionally associated with specific culturable pathogens, are unique or shared with other chronic infections of the lower airways is not well studied. Little is also known about how these chronic infection microbiota change from childhood to adulthood. We sought to compare the core microbiota in respiratory specimens from children and adults with different chronic lung infections. We used bacterial 16S rRNA gene pyrosequencing, phylogenetic analysis, and ecological statistical tools to compare the core microbiota in respiratory samples from three cohorts of symptomatic children with clinically distinct airway diseases (protracted bacterial bronchitis, bronchiectasis, CF), and from four healthy children. We then compared the core pediatric respiratory microbiota with those in samples from adults with bronchiectasis and CF. All three pediatric disease cohorts shared strikingly similar core respiratory microbiota that differed from adult CF and bronchiectasis microbiota. The most common species in pediatric disease cohort samples were also detected in those from healthy children. The adult CF and bronchiectasis microbiota also differed from each other, suggesting common early infection airway microbiota that diverge by adulthood. The shared core pediatric microbiota included both traditional pathogens and many species not routinely identified by standard culture. Our results indicate that these clinically distinct chronic airway infections share common early core microbiota, which are likely shaped by natural aspiration and impaired clearance of the same airway microbes, but that disease-specific characteristics select for divergent microbiota by adulthood. Longitudinal and interventional studies will be required to define the relationships between microbiota, treatments, and disease progression.

What is chronic cough in children?

The cough reflex is modulated throughout growth and development. Cough—but not expiration reflex—appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.

Drug treatments of childhood coughs

Appropriate management of cough in children depends upon accurate assessment. The diagnosis is often unclear at the initial presentation. Acute cough is frequently caused by a viral infection, and often no specific therapy is indicated. Urgent treatment may be needed if history suggests a more serious disorder such as a foreign body or pneumonia. When treating children with chronic cough, paediatric-specific algorithms should be used . Empirical use of medicines without looking for a specific cause should be avoided. In the absence of an alternative specific cause of cough, chronic wet cough (lasting at least four weeks) is most frequently due to protracted bacterial bronchitis. Antibiotics are indicated.

Prospective Characterization of Protracted Bacterial Bronchitis in Children

BackgroundPrior studies on protracted bacterial bronchitis (PBB) in children have been retrospective or based on small cohorts. As PBB shares common features with other pediatric conditions, further characterization is needed to improve diagnostic accuracy among clinicians. In this study, we aim to further delineate the clinical and laboratory features of PBB in a larger cohort, with a specific focus on concurrent viral detection.MethodsChildren with and without PBB (control subjects) undergoing flexible bronchoscopy were prospectively recruited. Basic immune function testing and lymphocyte subset analyses were performed. BAL specimens were processed for cellularity and microbiology. Viruses were identified using polymerase chain reaction (PCR) and bacteria were identified via culture.ResultsThe median age of the 104 children (69% male) with PBB was 19 months (interquartile range [IQR], 12-30 mo). Compared with control subjects, children with PBB were more likely to have attended childcare (OR, 8.43; 95% CI, 2.34-30.46). High rates of wheeze were present in both groups, and tracheobronchomalacia was common. Children with PBB had significantly elevated percentages of neutrophils in the lower airways compared with control subjects, and adenovirus was more likely to be detected in BAL specimens in those with PBB (OR, 6.69; 95% CI, 1.50-29.80). Median CD56 and CD16 natural killer (NK) cell levels in blood were elevated for age in children with PBB (0.7 × 109/L; IQR, 0.5-0.9 cells/L).ConclusionsChildren with PBB are, typically, very young boys with prolonged wet cough and parent-reported wheeze who have attended childcare. Coupled with elevated NK-cell levels, the association between adenovirus and PBB suggests a likely role of viruses in PBB pathogenesis.

Chronic 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.

Adenovirus species C is associated with chronic suppurative lung diseases in children.

The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(-)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38-7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.

Differential diagnosis of chronic cough in children

A cough is considered chronic when it lasts >4 weeks. Chronic cough can be from a variety of causes. This article provides a structured approach to evaluating the child with chronic cough. Beginning with the disturbing cough that is absent once asleep, consistent with the habit cough syndrome, the diagnostic criteria for 10 causes of chronic cough are discussed. Using a structured approach to the differential diagnosis, common and uncommon causes can be identified. Well-established causes of chronic cough, such as asthma, are likely to be well known to the reader, whereas more recently identified etiologies, such as protracted bacterial bronchitis, are presented in more detail. The differential value of flexible and rigid bronchoscopy and bronchoalveolar lavage for aiding in the differential diagnosis is included for those entities where their use is essential.

The assessment and management of chronic cough in children according to the British Thoracic Society guidelines: descriptive, prospective, clinical trial

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.

The Importance of Recognizing Protracted Bacterial Bronchitis in Children

The Importance of Recognizing Protracted Bacterial Bronchitis in Children

Chronic cough in preschool children

Cough may be the first overt sign of disease of the airways or lungs when it represents more than a defense mechanism, and may by its persistence become a helpful pointer of potential disease for both patient and physician. On the other hand, impairment or absence of the coughing mechanism can be harmful and even fatal; this is why cough suppression is rarely indicated in childhood. Pediatricians are concerned more with the etiology of the cough and making the right diagnosis. Whereas chronic cough in adults has been universally defined as a cough that lasts more than 8weeks, in childhood, different timing has been reported. Many reasons support defining a cough that lasts more than 4weeks in preschool children as chronic, however; and this is particularly true when the cough is wet. During childhood, the respiratory tract and nervous system undergo a series of anatomical and physiological maturation processes that influence the cough reflex. In addition, immunological response undergoes developmental and memorial processes that make infection and congenital abnormalities the overwhelming causes of cough in preschool children. Cough in children should be treated on the basis of etiology, and there is no evidence in support of the use of medication for symptomatic cough relief or adopting empirical approaches. Most cases of chronic cough in preschool age are caused by protracted bacterial bronchitis, tracheobronchomalacia, foreign body aspiration, post-infectious cough or some combination of these. Other causes of chronic cough, such as bronchiectasis, asthma, gastroesophageal reflux, and upper respiratory syndrome appear to be less frequent in this age group. The prevalence of each depends on the population in consideration, the epidemiology of infectious diseases, socioeconomic aspects, and the local health system.

Managing children with protracted bacterial bronchitis

AbstractOur series Prescribing in children gives practical advice for the successful management of childhood problems in general practice. Here, the authors discuss the diagnosis of protracted bacterial bronchitis and its management.

Children with “chronic wet cough” (presumed protracted bacterial bronchitis) respond to 14 days of amoxicillin clavulanate

Children with “chronic wet cough” (presumed protracted bacterial bronchitis) respond to 14 days of amoxicillin clavulanate