Chronic wet cough in Australian children: Societal costs and quality of life.

INTRODUCTION: Children with chronic wet cough regularly use the health system, experience considerable variability in care, have reduced quality of life (QoL), and, left untreated, poorer health outcomes. Despite this, little is known about the associated economic burden. This study aimed to quantify the cost of chronic wet cough among Australian children from the perspectives of families and the health system. METHODS: A cost of illness study was conducted at the Queensland Children's Hospital, Brisbane, using data on 91 children newly referred to a respiratory specialist between July 2015 and January 2017 with a history of chronic wet cough (>4 weeks) of unknown etiology. Administrative and parent-reported data were used to estimate costs (reported in 2019 Australian Dollars [AUD]) for up to 12 months before and following initial pulmonology consultation. QoL was assessed for the same periods. RESULTS: Mean cost per child-month during the average 9.8 months of observation preceding pulmonology consultation was AUD689 (95% confidence interval [CI] 534-844) increasing to AUD1339 (95% CI 1051-1628) during the average 11.9 months following pulmonology consultation. This translated to a total of AUD1.9 million across the study period, with families bearing 26.4% of costs. Aspiration and bronchiectasis were associated with higher total costs. For all etiologies, cough-specific QoL improved following pulmonology consultation, while direct medical costs declined. CONCLUSION: Childhood chronic wet cough is associated with substantial societal costs. The observed cost decrease after specialist diagnosis suggests that early referral to a respiratory specialist may have economic benefits, in addition to the known health benefits.

Development of a quality improvement audit tool for the primary care of children with chronic wet cough using a modified Delphi consensus approach.

AIM: In the absence of quality indicators (QIs) for the management of chronic wet cough, our study's aim was to determine whether consensus on QIs reflecting good primary health care, prior to referral for children with chronic wet cough, can be achieved. METHODS: A questionnaire consisting of 10 QIs was developed by a clinical working group based on current evidence and guidelines on the management of chronic wet cough in children. Each indicator reflected the quality of care provided to children with chronic wet cough in primary care prior to referral. A modified Delphi consensus questionnaire was undertaken involving expert paediatric respiratory clinicians and general paediatricians who graded the importance of each indicator for the purposes above. We a priori defined that consensus was considered achieved if >75% agreed on the indicator. RESULTS: Twenty-two specialists (from Brisbane, Melbourne, Perth and Canberra) participated in the survey. The cumulative number of years of their respiratory experience was 324 and that of general clinical practice was 504. Consensus was achieved in all 10 QIs, with 6 reaching 100% agreement. Mean agreement for the 10 items was 97%. CONCLUSION: As complete consensus was achieved on these QIs, it can be used as a provisional clinical audit tool and can guide the development of a robust audit tool for primary care clinical practice to assist with quality improvement initiatives.

Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis.

Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1ß expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1ß axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1ß-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1ß expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1ß secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1ß. NTHi stimulation induced formation of specks of cleaved IL-1ß, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1ß-dominated inflammation in PBB.