Ian B. Masters

Persistent cough in children and the overuse of medications

Objective:  Children referred for persistent cough were evaluated for the referring and final diagnosis, and the extent of the use of medications prior to referral and the side effects encountered.

Utility of signs and symptoms of chronic cough in predicting specific cause in children

Background: Paediatricians rely on cough descriptors to direct them to the level of investigations needed for a child presenting with chronic cough, yet there is a lack of published data to support this approach. A study was undertaken to evaluate (1) whether historical cough pointers can predict which children have a specific cause for their cough and (2) the usefulness of chest radiography and spirometry as standard investigations in children with chronic cough. Methods: This was a prospective cohort study of children referred to a tertiary hospital with a cough lasting >3 weeks between June 2002 and July 2004. All included children completed a detailed history and examination using a standardised data collection sheet and followed a pathway of investigation until a diagnosis was made. Results: In 100 consecutively recruited children of median age 2.8 years, the best predictor of specific cough observed was a moist cough at the time of consultation with an odds ratio (OR) of 9.34 (95% CI 3.49 to 25.03). Chest examination or chest radiographic abnormalities were also predictive with OR 3.60 (95% CI 1.31 to 9.90) and 3.16 (95% CI 1.32 to 7.62), respectively. The most significant historical pointer for predicting a specific cause of the cough was a parental history of moist cough (sensitivity 96%, specificity 26%, positive predictive value 74%). Conclusions: The most useful clinical marker in predicting specific cough is the presence of a daily moist cough. Both chest examination and chest radiographic abnormalities are also useful in predicting whether children have a specific cause of their cough.

Altered arousal response in infants exposed to cigarette smoke

Aims: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. Methods: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8–12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10–12 hours using complex sleep polysomnography. Results: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. Conclusion: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk of SIDS.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough

Background Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. Methods 50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was ‘cough resolution’ defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Results Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. Conclusion A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children. Clinical trial number ACTRN 12605000533695.

Clinical signs and symptoms of oropharyngeal aspiration and dysphagia in children

The diagnostic value of various signs and symptoms (clinical markers) in predicting oropharyngeal aspiration (OPA) or swallowing dysfunction has not been established in children. The present retrospective study was undertaken to: 1) identify specific clinical markers associated with radiographic evidence of OPA, isolated laryngeal penetration (ILP) and post-swallow residue (PSR); 2) determine the sensitivity and specificity of clinical markers associated with OPA; and 3) determine the influence of age and neurological impairment on clinical markers of OPA. In total, 11 clinical markers of dysphagia were compared with the videofluoroscopic swallow study (VFSS) results (OPA, ILP and PSR) in 150 children on diets of thin fluid and purée consistencies. Chi-squared and logistic regression were used to analyse the association between clinical markers and VFSS-identified swallowing dysfunction. In children with OPA, wet voice (odds ratio (OR) 8.90, 95% confidence interval (CI) 2.87–27.62), wet breathing (OR 3.35, 95% CI 1.09–10.28) and cough (OR 3.30, 95% CI 1.17–9.27) were significantly associated with thin fluid OPA. Predictive values included: wet voice (sensitivity 0.67; specificity 0.92); wet breathing (sensitivity 0.33; specificity 0.83); and cough (sensitivity 0.67; specificity 0.53). No clinical markers were significantly associated with OPA, ILP or PSR on the purée consistency. Cough was significantly associated with PSR on thin fluids (OR 3.59, 95% CI 1.22–10.55). Differences were found for age. Wet voice, wet breathing and cough were good clinical markers for children with oropharyngeal aspiration on thin fluid but not on purée. Age and neurological status influenced the significance of these clinical markers.

Application of chest high‐resolution computer tomography in young children with cystic fibrosis

Summary. High‐resolution computed tomography (HRCT) of the chest permits early detection of lung disease; two relevant scoring systems (Bhalla and Nathanson) have been developed to describe CF lung disease. Comparisons between the two scoring systems have not been made, and it is not known which system is more appropriate for young children, i.e., the age group where other objective markers are scarce. We reviewed the clinical findings, pulmonary function data, and HRCT of 16 children aged less than 12 years.

Longitudinal Growth and Lung Function in Pediatric Non-Cystic Fibrosis Bronchiectasis: What Influences Lung Function Stability?

BACKGROUND Longitudinal FEV(1) data in children with non-cystic fibrosis (non-CF) bronchiectasis (BE) are contradictory, and there are no multifactor data on the evolution of lung function and growth in this group. We longitudinally reviewed lung function and growth in children with non-CF BE and explored biologically plausible factors associated with changes in these parameters over time. METHODS Fifty-two children with > or = 3 years of lung function data were retrospectively reviewed. Changes in annual anthropometry and spirometry at year 3 and year 5 from baseline were analyzed. The impact of sex, age, cause, baseline FEV(1), exacerbation frequency, radiologic extent, socioeconomic status, environmental tobacco smoke exposure, and period of diagnosis was evaluated. RESULTS Over 3 years, the group mean forced expiratory flow midexpiratory phase percent predicted and BMI z-score improved by 3.01 (P = .04; 95% CI, 0.14-5.86) and 0.089 (P = .01; 95% CI, 0.02-0.15) per annum, respectively. FEV(1)% predicted, FVC% predicted, and height z-score all showed nonsignificant improvement. Over 5 years, there was improvement in FVC% predicted (slope 1.74; P = .001) annually, but only minor improvement in other parameters. Children with immunodeficiency and those with low baseline FEV(1) had significantly lower BMI at diagnosis. Frequency of hospitalized exacerbation and low baseline FEV(1) were the only significant predictors of change in FEV(1) over 3 years. Decline in FEV(1)% predicted was large (but nonsignificant) for each additional year in age of diagnosis. CONCLUSIONS Spirometric and anthropometric parameters in children with non-CF BE remain stable over a 3- to 5-year follow-up period once appropriate therapy is instituted. Severe exacerbations result in accelerated lung function decline. Increased medical cognizance of children with chronic moist cough is needed for early diagnosis, better management, and improving overall outcome in BE.

Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease

Background: Published data on the frequency and types of flexible bronchoscopic airway appearances in children with non-cystic fibrosis bronchiectasis and chronic suppurative lung disease are unavailable. The aims of this study were to describe airway appearances and frequency of airway abnormalities and to relate these airway abnormalities to chest high resolution computed tomography (cHRCT) findings in a cohort of children with non-cystic fibrosis chronic suppurative lung disease (CSLD). Methods: Indigenous children with non-cystic fibrosis CSLD (>4 months moist and/or productive cough) were prospectively identified and collected over a 2.5 year period at two paediatric centres. Their medical charts and bronchoscopic notes were retrospectively reviewed. Results: In all but one child the aetiology of the bronchiectasis was presumed to be following a respiratory infection. Thirty three of the 65 children with CSLD underwent bronchoscopy and five major types of airway findings were identified (mucosal abnormality/inflammation only, bronchomalacia, obliterative-like lesion, malacia/obliterative-like combination, and no macroscopic abnormality). The obliterative-like lesion, previously undescribed, was present in 16.7% of bronchiectatic lobes. Structural airway lesions (bronchomalacia and/or obliterative-like lesion) were present in 39.7% of children. These lesions, when present, corresponded to the site of abnormality on the cHRCT scan. Conclusions: Structural airway abnormality is commonly found in children with post-infectious bronchiectasis and a new bronchoscopic finding has been described. Airway abnormalities, when present, related to the same lobe abnormality on the cHRCT scan. How these airway abnormalities relate to aetiology, management strategy, and prognosis is unknown.

A Cough Algorithm for Chronic Cough in Children: A Multicenter, Randomized Controlled Study

OBJECTIVES The goals of this study were to: (1) determine if management according to a standardized clinical management pathway/algorithm (compared with usual treatment) improves clinical outcomes by 6 weeks; and (2) assess the reliability and validity of a standardized clinical management pathway for chronic cough in children. METHODS: A total of 272 children (mean ± SD age: 4.5 ± 3.7 years) were enrolled in a pragmatic, multicenter, randomized controlled trial in 5 Australian centers. Children were randomly allocated to 1 of 2 arms: (1) early review and use of cough algorithm (“early-arm”); or (2) usual care until review and use of cough algorithm (“delayed-arm”). The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6. Secondary measures included cough duration postrandomization and the algorithm’s reliability, validity, and feasibility. RESULTS: Cough resolution (at week 6) was significantly more likely in the early-arm group compared with the delayed-arm group (absolute risk reduction: 24.7% [95% confidence interval: 13–35]). The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group (mean difference between groups: 0.6 [95% confidence interval: 0.29–1.0]). Duration of cough postrandomization was significantly shorter in the early-arm group than in the delayed-arm group (P = .001). The cough algorithm was reliable (κ = 1 in key steps). Feasibility was demonstrated by the algorithm’s validity (93%–100%) and efficacy (99.6%). Eighty-five percent of children had etiologies easily diagnosed in primary care. CONCLUSIONS: Management of children with chronic cough, in accordance with a standardized algorithm, improves clinical outcomes irrespective of when it is implemented. Further testing of this standardized clinical algorithm in different settings is recommended.

A new method for objective identification and measurement of airway lumen in paediatric flexible videobronchoscopy

Background: Accurate measurements of airway and lesion dimensions are important to the developmental progress of paediatric bronchoscopy. The malacia disorders are an important cause of respiratory morbidity in children, but no methods are currently available to measure these lesions or the airway lumen accurately. A new measurement technique is described here. Methods: The magnification power of a paediatric videobronchoscope was defined and a simple and user friendly computer based program (Image J) was used to develop an objective technique (colour histogram mode technique, CHMT) for measurement of the airway lumen. Results: In vivo intra-observer and inter-observer repeatability coefficients for repeated area measurements from 28 images using the Bland-Altman method were 0.9 mm2 and 1.6 mm2, respectively. The average intraclass correlation coefficient for repeated measurements of area was 0.93. In vitro validation measurements using a 2 mm diameter tube resolved radii measurements to within 0.1 mm (coefficient of variability 8%). An “acceptable result” was defined in 92% of 734 images completed with the CHMT alone and 8% with its modification. The success rate for two of three images being within 10% of each other’s area was 100%. Measurements of cricoid cross sectional areas from 116 patients compared with expected airway areas for age derived from endotracheal tube sizes were comparable. Conclusions: The CHMT method of identifying and measuring airway dimensions is objective, accurate, and versatile and, as such, is important to the future development of flexible videobronchoscopy.