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IntroductionNusinersen is used in spinal muscular atrophy (SMA) to improve peripheral muscle function; however, respiratory effects are largely unknown.AimTo assess the effects of nusinersen on respiratory function in paediatric SMA during first year of treatment.MethodsA prospective observational study in paediatric patients with SMA who began receiving nusinersen in Queensland, Australia, from June 2018 to December 2019. Outcomes assessed were the age-appropriate respiratory investigations: spirometry, oscillometry, sniff nasal inspiratory pressure, mean inspiratory pressure, mean expiratory pressure, lung clearance index, as well as polysomnography (PSG) and muscle function testing. Lung function was collected retrospectively for up to 2 years prior to nusinersen initiation. Change in lung function was assessed using mixed effects linear regression models, while PSG and muscle function were compared using the Wilcoxon signed-rank test.ResultsTwenty-eight patients (15 male, aged 0.08–18.58 years) were enrolled: type 1 (n=7); type 2 (n=12); type 3 (n=9). The annual rate of decline in FVC z-score prior to nusinersen initiation was −0.58 (95% CI −0.75 to −0.41), and post initiation was −0.25 (95% CI −0.46 to −0.03), with a significant difference in rate of decline (0.33 (95% CI 0.02 to 0.66) (p=0.04)). Most lung function measures were largely unchanged in the year post nusinersen initiation. The total Apnoea–Hypopnoea Index (AHI) was reduced from a median of 5.5 events/hour (IQR 2.1–10.1) at initiation to 2.7 events/hour (IQR 0.7–5.3) after 1 year (p=0.02). All SMA type 1% and 75% of SMA types 2 and 3 had pre-defined peripheral muscle response to nusinersen.ConclusionThe first year of nusinersen treatment saw reduced lung function decline (especially in type 2) and improvement in AHI.

Background Sleep disordered breathing (SDB) causes sleep disturbance and daytime symptoms in children with neuromuscular disorders. Although polysomnography (PSG) findings are well described in many neuromuscular disorders, there are limited reports from children with spinal muscular atrophy (SMA). The aim of this study was to determine the sleep architecture and breathing characteristics and non-invasive ventilation (NIV) use in our pediatric SMA cohort. Methods We conducted a cross-sectional cohort study of all children with SMA in Queensland, Australia. Children were Nusinersen naive and had a full diagnostic PSG in 2018. The PSG was scored and reported by a single pediatric sleep physician in accordance with American Academy of Sleep Medicine Criteria (2012). Results In sum, 31 children (18 males), Six with Type 1, 16 with Type 2 and nine with Type 3, aged 0.25–18.8 years old were studied. SDB was seen in each SMA type and was more pronounced during rapid eye movement (REM) sleep. Type 1: all patients exhibited SDB, three (50%) with central sleep apnea (CSA) and three (50%) with mixed disease. Type 2: five (31%) had CSA, one (6%) mixed disease, seven (44%) had early SDB and three (19%) had normal sleep breathing. Type 3: four (44%) children had CSA and five had early SDB. No child exhibited obstructive sleep apnea (OSA) alone.Starting NIV significantly reduced mean total PSG Apnea-Hypopnea Index (AHI) scores from a grouped mean of 15.4 events per hour (SD ± 14.6; 95% CI 6.1–24.7) to 4.0 events per hour (SD ± 4.2, 95% CI 1.2–6.5, p = 0.01). Conclusion SDB is common in children with SMA and was present in all types. CSA was the most common disorder; with mixed SDB also present in type 1 and 2 SMA.

Mycobacterium abscessus complex pulmonary disease (M. abscessus PD) in cystic fibrosis (CF) is challenging to treat. Current guideline therapeutic regimens involving an intensive phase of intravenous (IV) antibiotics followed by a consolidation phase of inhaled and oral antibiotics are not evidence-based. The objectives of this study were to characterize the clinical outcomes and clearance of Mycobacterium abscessus complex (M. abscessus) from respiratory cultures in children with CF M. abscessus PD.This retrospective longitudinal cohort analysis evaluated the first course of treatment for M. abscessus PD in 33 children in Queensland, Australia between 2001 and 2015. Spirometry and nutritional outcomes 2 years pretreatment and 1 year posttreatment were compared with clearance or relapse/persistence of Mycobacterium abscessus complex from respiratory cultures.Nine of 18 children who completed therapy, cleared infection. Three of 7 children who completed only intensive therapy cleared sputum compared with 0/8 children who did not. The trajectory of the percent predicted forced expiratory volume in 1 s and age standardized body mass index significantly improved posttreatment in those that cleared sputum (P0.0001).These results suggest that current treatment recommendations for M. abscessus PD are associated with some success in clearing infection in children with CF and improvement in lung function and body mass index. Clinical trials are required to determine the best treatment approaches.

Purpose of review Aspergillus spp. cause a clinical spectrum of disease with severity of disease dependent on degree of immune compromise, nature and intensity of inflammatory host response, and/or underlying lung disease. Chronic pulmonary aspergillosis encompasses a spectrum of diseases including aspergilloma, Aspergillus nodules, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, and subacute invasive pulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) paradoxically is an immune hypersensitivity manifestation in the lungs that almost always occurs in the setting of underlying asthma or cystic fibrosis. These chronic Aspergillus conditions are now becoming more prevalent than invasive Aspergillus, thus it is important to be aware of the current literature of these conditions. Recent findings High-level research assessing the clinical significance and treatment options of these chronic diseases are lacking. Recent literature suggests colonization is antecedent for local airway infection (Aspergillus bronchitis), chronic or allergic bronchopulmonary disease, or invasive and potentially disseminated disease. There have been few advances in assessment of treatment of ABPA. Summary Research assessing the clinical significance and treatment options is currently needed.

We have witnessed a change in disease patterns contributing to the global burden of disease, with a shift from early childhood deaths due to the classic infectious communicable diseases to years lived with disability from chronic noncommunicable diseases. In both developing and developed countries, the years lived with disability attributable to chronic disease have increased: cardiovascular diseases by 17.7%; chronic respiratory disease by 8.5%; neurological conditions by 12.2%; diabetes by 30.0%; and mental and behavioural disorders by 5.0% over the past 20 years. Recognition of the contribution made by adverse environmental exposures in early life to noncommunicable diseases in later life is increasing. These early-life exposures appear to contribute to both chronic respiratory and chronic nonrespiratory diseases. In this State of the Art article, we aim to examine early-life environmental exposures that have an epidemiological association with chronic nonrespiratory diseases, such as obesity and type II diabetes, cardiovascular disease, and neurocognitive and behavioural problems. We will highlight the potential overlap in environmental risks with respiratory diseases, and point out knowledge gaps and research opportunities.

Rationale Individual assessment of airway obstruction in preschool-age children requires sensitive and specific lung function methods with low demand of cooperation. Although the forced oscillation technique (FOT) is feasible in young children, conventional measurements of respiratory impedance (Zrs) have limited diagnostic power in individuals. Objective To find descriptors of within-breath Zrs that are sensitive indicators of airway obstruction during tidal breathing in children. Methods Zrs was measured with (i) a standard multifrequency FOT (4–26 Hz) to assess the mean values of resistance and reactance for whole breaths and (ii) a 10 Hz signal to track the within-breath changes. Various Zrs measures obtained in healthy children (n=75) and those with acute wheeze (n=31) were investigated with receiver operator characteristic (ROC) analysis. The cut-off values obtained for airway obstruction were then tested in children with recurrent wheeze (n=20) before and after administration of salbutamol. Results The largest area under the ROC curve (0.95) was observed for the tidal changes of resistance between the zero-flow values (ΔR). The ΔR cut-off value of 1.42 hPa s/L detected airway obstruction with sensitivity of 92% and specificity of 89% in children with acute wheeze and distinguished children with recurrent wheeze (16/20 above the cut-off value) from healthy children (22/23 below the cut-off value). Furthermore, ΔR significantly decreased after salbutamol in wheezy children but remained unchanged in healthy children. Conclusions New lung function measure ΔR is able to detect airway obstruction with high sensitivity and specificity and is suitable for use in lung function testing in young children.