European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease.

There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3-17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels >1 mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.

Chronic Aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function.

Filamentous fungi are commonly isolated from the respiratory tract of CF patients, but their clinical significance is uncertain and the reported incidence variable. We report on the degree of Aspergillus fumigatus airway colonization in a tertiary pediatric CF cohort, evaluate the sensitivity of routine clinical sampling at detecting A. fumigatus, and compare lung function of A. fumigatus-colonized and non-colonized children.We carried out an 8-year retrospective cohort analysis using local databases, examining 1024 respiratory microbiological specimens from 45 children. Nineteen (42%) had a positive A. fumigatus culture at least once during the 8-year period, with 10 (22%) children persistently colonized. Overall, 29% of 48 bronchoalveolar lavage (BAL) samples tested positive for A. fumigatus, compared with 14% of 976 sputum samples. Of 33 children for whom lung function data were available during the study period, seven were classed as having severe lung disease, of whom four (57%) were persistently colonized with A. fumigatus.We conclude that chronic A. fumigatus colonization of the CF airway is common, and may be associated with worse lung function. In our practice, BAL appears superior at detecting lower airway A. fumigatus compared to sputum samples.

Early detection of non-tuberculous mycobacteria in children with cystic fibrosis using induced sputum at annual review.

AIM: Non-tuberculous mycobacteria (NTM) have emerged as an important pathogen in cystic fibrosis (CF). Early detection and treatment of NTM can preserve lung function and maintain good lung health. Many children with CF are not regular sputum producers and cough swabs cannot routinely be used to diagnose NTM. We aimed to test the hypothesis that performing sputum induction at routine annual review results in earlier identification of NTM in non-sputum producing children with CF. METHOD: We conducted a 5-year prospective observational cohort study involving children with CF aged 5-17 years who had sputum induction with hypertonic saline for microbiological surveillance including NTM at their annual review. RESULTS: Forty-two children (19 males, mean age 11.4 years ± 3.6, mean FEV1 % predicted 94.7 ± 20.6) participated in the study. Forty-one induced sputum samples from 29 children yielded bacterial pathogens. Six samples from six children (14% of the cohort) yielded NTM never previously isolated from the patient. We also detected three isolates of Pseudomonas aeruginosa and one isolate each of Burkholderia cepacia complex and Meticillin resistant Staphylococcus aureus (MRSA), all of which were first time isolates. CONCLUSION: We conclude that annual induced sputum for microbiological surveillance is useful for early detection of NTM and other important respiratory pathogens, particularly in non-expectorating children. This may lead to earlier identification and help inform initiation of eradication treatment in children with NTM. Children can also be cohorted earlier, before they potentially infect other children in the clinic.