Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1b is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1b requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1b endotype associated with the nucleotide-binding domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic subtype of asthma.Participants with asthma (n585) and healthy controls (n527) underwent clinical assessment, spirometry and sputum induction. Sputum was processed for differential cell count, gene expression and protein mediators. NLRP3 and caspase-1 expression was also determined by immunocytochemistry. Sputum macrophages were isolated (n58) and gene expression of NLRP3 and IL-1b determined.There was significantly elevated gene expression of NLRP3, caspase-1, caspase-4, caspase-5 and IL-1b in participants with neutrophilic asthma. Protein levels of IL-1b were significantly higher in those with neutrophilic asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein.NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the inflammation process observed in this asthma phenotype through production of IL-1b. @ERSpublications The NLRP3 inflammasome may be a key regulator of neutrophilic airway inflammation in asthma through production of IL-1b

Inflammatory phenotypes are recognised in stable adult asthma, but are less well established in childhood and acute asthma. Additionally, Chlamydophila pneumoniae infection as a cause of noneosinophilic asthma is controversial. This study examined the prevalence of inflammatory phenotypes and the presence of current C. pneumoniae infection in adults and children with stable and acute asthma.Adults with stable (n529) or acute (n522) asthma, healthy adults (n511), children with stable (n549) or acute (n528) asthma, and healthy children (n59) underwent clinical assessment and sputum induction. Sputum was assessed for inflammatory cells, and DNA was extracted from sputum cell suspensions and supernatants for C. pneumoniae detection using real-time PCR.The asthma phenotype was predominantly eosinophilic in children with acute asthma (50%) but neutrophilic in adults with acute asthma (82%). Paucigranulocytic asthma was the most common phenotype in both adults and children with stable asthma. C. pneumoniae was not detected in 99% of samples.The pattern of inflammatory phenotypes differs between adults and children, with eosinophilic inflammation being more prevalent in both acute and stable childhood asthma, and neutrophilic inflammation being the dominant pattern of acute asthma in adults. The aetiology of neutrophilic asthma is unknown and is not explained by the presence of current active C. pneumoniae infection.

In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development.

Neutrophilic airway inflammation is associated with increased HAT and reduced HDAC activity in blood monocytes, demonstrating further systemic manifestations relating to the altered inflammatory gene transcription profile of neutrophilic asthma.