Background: Distinguishing phenotypes among children with cough helps understand underlying causes. Using a statistical data-driven approach, we identified cough phenotypes and we aimed to validate them based on measurable traits, physician diagnoses, and prognosis. Methods: We used data from 531 children aged 5-16 years from the Swiss Paediatric Airway Cohort - a multicentre clinical cohort of children seen in outpatient clinics since 2017. We included children with any parent-reported cough (i.e. cough without a cold, cough at night, cough more than others, or cough longer than 4 weeks) without current wheeze. We applied latent class analysis to identify phenotypes using 9 symptoms and characteristics and selected the best model using the Akaike Information Criterion. We assigned children to the most likely phenotype and compared the resulting groups with regards to parental history, comorbidities, measurable traits, physician diagnoses, and prognosis after 1 year. Results: Our analysis distinguished 4 cough phenotypes: 1. unspecific dry cough (25%); 2. non-allergic infectious and night cough with snoring and otitis (4%); 3. allergic dry night cough with snoring (9%); and 4. allergic cough (61%). Children with the allergic phenotype often had family or personal history of atopy and were diagnosed with asthma. Fractional exhaled nitric oxide was highest for the allergic phenotype [median 17.9 parts per billion (ppb)] and lowest for the non-allergic infectious phenotype (median 7.0 ppb). Positive allergy test results differed across phenotypes (p<0.001) and were most common among the allergic (70%) and least common among the unspecific dry cough (31%) phenotypes. Subsequent wheeze was thrice as high among the allergic than the unspecific dry cough phenotype. Conclusion: We distinguished 4 clinically-relevant cough phenotypes; they differed by measurable traits, physician diagnoses, and prognosis. Although we excluded children with current wheeze, most children belonged to allergy-related phenotypes and possibly need allergy and asthma work-ups.

MCM, ESLP, RM, AJ, MG, BDS, and CK have nothing to disclose. SB reports meeting/travelling fees from OM Pharma and Novartis-all outside the submitted work. KH reports personal fees from Astra Zeneca-all outside the submitted work. PL reports personal fees from OM Pharma, Polyphor, Santhera, Vertex, Vifor, Sanofi Aventis, and grants from Vertex-all outside the submitted work. AM reports personal fees from Vertex, OM Pharma, Astra Zeneca, and grants from Vertex- all outside the submitted work. NR reports personal fees from OM Pharma, Astra Zeneca, Schwabe Pharma, and Sanofi-all outside the submitted work.

The Swiss National Science Foundation (SNF Grants: SNF 320030_182628 & SNF 320030_212519) funded the study. Myrofora Goutaki is funded by an SNF Ambizione Fellowship (PZ00P3_185923).

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The Bern Cantonal Ethics Committee (Kantonale Ethikkomission Bern 2016-02176) gave ethical approval for this work

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