{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T09:29:47Z","timestamp":1786958987809,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epidemiologia"],"abstract":"<jats:p>Background\/Objective: Obesity has been linked to a distinct non-allergic, late-onset, neutrophilic asthma phenotype for more than two decades, yet whether obesity should be regarded as a cause of that phenotype rather than a coexisting comorbidity remains unresolved because randomised allocation to obesity is neither feasible nor ethical. This review asks whether the evidence accumulated between 1995 and 2026 supports a causal interpretation. Methods: A structured narrative synthesis was undertaken. PubMed\/MEDLINE, Scopus and Web of Science were searched from January 1995 to June 2026 (the synthesis emphasises the 2020\u20132026 evidence while drawing on the full window for landmark studies) for cohort, cross-sectional, Mendelian randomisation (MR), interventional, mechanistic and pharmaco-epidemiological studies; landmark earlier work was retained where it remains the primary source for a given viewpoint. The retrieved evidence was mapped onto Sir Austin Bradford Hill\u2019s nine viewpoints (1965) and triangulated using E-values for unmeasured confounding, GRADE, directed acyclic graphs and MR. Results: All nine viewpoints were satisfied to varying degrees. Strength: effect estimates 1.4\u20136.8, E-values 4.8\u201313.1, MR summary risk ratio 1.05 per 1 kg\/m2. Consistency: replication across four continents, both sexes and multiple study designs. Temporality: prospective cohort and life-course MR evidence. Biological gradient: body mass index dose\u2013response for TNF\u03b1, IL-17A and Th17 frequency. Plausibility: a twelve-layer architecture from adipose dysfunction to bronchial epithelium. Coherence, experimental evidence (bariatric surgery, lifestyle weight loss, GLP-1 receptor agonists, murine and in vitro models) and analogy were also supported; specificity was met at the phenotype level. Conclusions: The cumulative evidence strongly supports a causal contribution of obesity to the development of the late-onset, non-allergic asthma phenotype while falling short of definitive proof (GRADE: moderate certainty), with implications for primary prevention, endotype-targeted therapy and longitudinal research. Phenotype-stratified MR remains the principal missing element of the causal argument.<\/jats:p>","DOI":"10.3390\/epidemiologia7040107","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:08:02Z","timestamp":1786003682000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Inference in Non-Allergic Asthma Associated with Obesity: Application of the Bradford Hill Viewpoints to a Complex Epidemiological Association"],"prefix":"10.3390","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-1786","authenticated-orcid":false,"given":"Jos\u00e9 J.","family":"Leija-Martinez","sequence":"first","affiliation":[{"name":"Hospital Regional de Alta Especialidad \u201cDr. Ignacio Morones Prieto\u201d, IMSS-Bienestar, Av. Venustiano Carranza No. 2395, San Luis Potosi C.P. 78290, San Luis Potosi, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5474-7500","authenticated-orcid":false,"given":"Eduardo","family":"Ensaldo-Carrasco","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones en Ergonom\u00eda, Centro Universitario de Arte, Arquitectura y Dise\u00f1o (CUAAD), Universidad de Guadalajara, Calzada Independencia Norte No. 5075, Guadalajara 44250, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-1632","authenticated-orcid":false,"given":"Fausto","family":"S\u00e1nchez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-8869","authenticated-orcid":false,"given":"Blanca E.","family":"Del-R\u00edo-Navarro","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Alergia e Inmunolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Dr. M\u00e1rquez 162, Cuauhtemoc, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-7517","authenticated-orcid":false,"given":"Nayely","family":"Reyes-Noriega","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Alergia e Inmunolog\u00eda, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Dr. M\u00e1rquez 162, Cuauhtemoc, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6503-694X","authenticated-orcid":false,"given":"Fengyang","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Obesidad y Asma, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","first-page":"295","article-title":"The environment and disease: Association or causation?","volume":"58","author":"Hill","year":"1965","journal-title":"Proc. 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