Introduction: There is substantial overlap between COPD, asthma, bronchiectasis(BE) and cystic fibrosis(CF) and each is characterised by inflammation and mucociliary dysfunction.

Hypothesis: Biology, rather than disease labels, may stratify patients into therapeutically relevant subtypes.

Methods: Patients were categorized by primary disease and clinical characteristics, spontaneous  sputum was collected and inflammatory characteristics (neutrophil elastase(NE) and 19 cytokines) and sputum properties (DNA content, mucins, rheology, dry weight) measured. K-means clustering was performed and parameters compared between and within disease groups. Smokers without respiratory disease were used as controls.

Results: The study included patients with asthma(76), COPD(91), BE(54), CF(24) and controls(26). 10 cytokines, NE, dry weight, mucins and multiple sputum parameters were different between disease groups and healthy controls (p<0.05). K means clustering identified 2 clusters defined by neutrophilic (N) or eosinophilic (E) inflammation. The E cluster was associated with lower dry weight, DNA content and higher mucins, particularly MUC5B. The rheology parameters G? and G* were significantly higher in the E group while Tan(delta) was higher in the N group (p<0.05 all comparisons). Both clusters were present in all disease groups with more neutrophilic inflammation in CF and BE (42% of COPD patients and 46% of asthma patients were neutrophilic vs 78% of BE and 87% of CF,p<0.0001).

Conclusion: Airways diseases have heterogenous inflammatory and mucus parameters. Assessment based on disease labels may be aided by endotyping using inflammatory and mucociliary clearance parameters.