Main characteristics of the observational studies included in the pairwise meta-analysis. When necessary, age, sex and smoking habit were reported as weighted arithmetic mean between asthma and nonasthma populations
| First author, year [ref.] | Country | Study characteristics | Duration of observation (years) | Subjects analysed | Asthmatic subjects | Groups of comparison | Subjects’ characteristics | Age (years) | Male (%) | Diagnosis of asthma | Current smokers (%) | NOS quality assessment | JBI checklist tool+ | |||
| Selection | Comparability | Outcome#/exposure¶ | Total | |||||||||||||
| Chalitsios, 2021 [49] | UK | Population-based, retrospective, longitudinal, cohort study | 13 | 658 749 | 138 123 (21.0) | Asthma versus nonasthma control | Subjects selected from the UK Clinical Practice Research Database | 51.8 | 41.0 | Read codes for asthma | 20.4 | **** | ** | ** | 8 | |
| Landré, 2020 [50] | France | Retrospective, cohort study | 26 | 12 345 | 372 (3.0) | Asthma versus nonasthma control | Subjects selected from the French GAZEL cohort of community-dwelling adults | 69.8 | 74.0 | Diagnosis defined by questionnaire | 7.0 | *** § | ƒ | 3 | ||
| Carter, 2019 [54] | UK | Retrospective, cohort study | ≈12 | 362 544 | 60 424 (16.7) | Asthma versus nonasthma control | Subjects admitted to NHS hospitals in the UK | 48.6 | 26.5 | Diagnostic ICD-10 and OPCS-4 disease codes | NA | *** § | ** | * ƒ | 6 | |
| Kim, 2019 [55] | Korea | Population-based, retrospective, longitudinal, cohort study | ≈11 | 226 118 | 113 059 (50.0) | Asthma versus nonasthma control | Subjects randomly selected from the Korean National Health Insurance Service Database | ≥20.0 | 37.3 | Asthma or status asthmaticus diagnostic ICD-10 codes: J45 or J46 of a physician diagnosis | NA | *** § | ** | * ƒ | 6 | |
| Kim, 2019 [40] | US | Population-based, retrospective, cross-sectional survey | ≈4 | 643 885 | 44 420 (6.9) | Asthma versus nonasthma control | Representative sample of civilian, non-institutionalised subjects of USA selected from the National Health Interview Survey | ≥18.0 | 48.0 | Diagnosis defined by questionnaire | 16.0 | High bias | ||||
| Bourdin, 2019 [63] | France | Population-based, retrospective, case–control study | 3 | 2760 | 690 (25.0) | Severe asthma versus nonasthma control | Subjects randomly selected from a French representative claims database | 61.0 | 34.3 | Diagnosis based on GINA recommendations (severe asthma patients received ≥1 dispensing for OMA and/or ≥10 dispensings of a medium or high dose of ICS+LABA) | NA | *** | ** | ** | 7 | |
| Toppila-Salmi, 2019 [64] | Finland | Population-based, retrospective, case–control study | 1 | 2890 | 1118 (38.7) | Asthma (includes severe asthma) versus nonasthma control | Subjects randomly selected from the Finnish Drug Reimbursement Register | 53.0 | 37.0 | Drug reimbursement decision of diagnosed asthma granted by prior physician's certificate, which includes background information, clinical examination results, lung function test results and findings and conclusions after asthma treatment test for 6 months | NA | *** | ** | * | 6 | |
| Varsano, 2017 [39] | Israel | Population-based, retrospective, cross-sectional study | 1 | 39 991 | 19 991 (50.0) | Nonsevere and severe asthma versus nonasthma control | Subjects selected from an Israeli population present in a national electronic healthcare insurance provider database | 42.2 | 23.8 | Asthma diagnostic ICD-9 CM code of a physician's diagnosis of bronchial asthma | 20.0 | Low bias | ||||
| Weatherburn, 2017 [38] | UK | Population-based, retrospective, cross-sectional study | NA | 1 424 378 | 84 505 (5.9) | Asthma versus nonasthma control | Representative sample of the Scottish population selected from the UK NHS database of primary care practice | ≥18.0 | 49.1 | Primary-care physician's diagnosis | 24.5 | Moderate bias | ||||
| Bozek, 2016 [37] | Poland | Population-based, retrospective, cross-sectional study | 1 | 2099 | 1023 (48.7) | Asthma versus nonasthma control | Representative population of all regions of Poland randomly selected from patient databases | 67.9 | 46.4 | Diagnosis based on clinical criteria according to GINA recommendations and a positive reversibility test after salbutamol according to the ATS/ERS criteria | 6.9 | Moderate bias | ||||
| Peng, 2015 [56] | Taiwan | Nationwide, retrospective, population-based, cohort study | ≈3 | 63 855 | 12 771 (20.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 53.7 | 45.8 | Asthma diagnostic ICD-9 CM code: 493 | NA | *** § | ** | * ƒ | 6 | |
| Van den Bemt, 2016 [57] | The Netherlands | Dynamic historical, longitudinal, cohort study | ≈20 | 2385 | 795 (33.3) | Asthma versus nonasthma control | Subjects selected from the Continuous Morbidity Registration Nijmegen database | 33.3 | 41.1 | Physician's diagnosis | NA | **** | ** | ** | 8 | |
| Yao, 2016 [58] | China | Population-based, retrospective, longitudinal, cohort study | 6 | 84 474 | 28 158 (33.3) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 54.5 | 46.3 | Asthma diagnostic ICD-9 CM code: 493; subjects who had ≥1 hospitalisation or ≥3 visits for outpatient medical services for asthma | NA | *** § | ** | * ƒ | 6 | |
| Cheng, 2015 [59] | Taiwan | Nationwide, retrospective, longitudinal, cohort study | 11 | 52 275 | 10 455 (20.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 59.8 | 41.3 | Asthma diagnostic ICD-9 CM code: 493; diagnosis by pulmonologist or rheumatologist on clinical judgement or pulmonary function test | NA | *** § | ** | * ƒ | 6 | |
| Alcázar Navarrete, 2015 [36] | Spain | Cross-sectional study | NA | 57 | 40 (70.2) | Asthma versus nonasthma control | Outpatients in an ambulatory setting | 60.8 | 31.6 | Previous physician diagnosis of bronchial asthma | 7.0 | Moderate bias | ||||
| Chung, 2014 [60] | Taiwan | Nationwide, retrospective, population-based, cohort study | 6 | 156 513 | 31 356 (20.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 38.9 | 49.0 | Asthma diagnostic ICD-9 code: 493 from ambulatory case visits or admission records | NA | *** § | ** | * ƒ | 6 | |
| Chung, 2014 [61] | Taiwan | Nationwide, retrospective, population-based, cohort study | 11 | 72 587 | 14 518 (20.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 52.1 | 45.7 | Asthma diagnostic ICD-9 CM code: 493 | NA | *** § | ** | * ƒ | 6 | |
| Steppuhn, 2014 [48] | Germany | Population-based, retrospective, cross-sectional survey | 2 | 43 189 | 2242 (5.2) | Asthma versus nonasthma control | Adults randomly selected for the national telephone health interview survey in Germany | 49.0 | 48.6 | Self-reported physician's diagnosis | 29.8 | Low bias | ||||
| Huang, 2014 [65] | Taiwan | Nationwide, prospective, population–based, case–control study (comorbidities were assessed retrospectively) | 3 | 140 344 | 35 086 (25.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 47.7 | 44.1 | Diagnosis by board-certified internist, clinical immunologist, pulmonologist or other medical experts | NA | **** | ** | ** | 8 | |
| Chen, 2014 [62] | Taiwan | Nationwide, retrospective, longitudinal, population-based, cohort study | 11 | 55 150 | 11 030 (20.0) | Asthma versus nonasthma control | Subjects randomly selected from the National Health Insurance Research Database of Taiwan | 60.9 | 41.7 | Asthma diagnostic ICD-9 CM code: 493 | NA | *** § | ** | * ƒ | 6 | |
| Sundbom, 2013 [47] | Sweden | Population-based, retrospective, cross-sectional survey | 1 | 25 610 | 1830 (7.1) | Asthma versus nonasthma control | Subjects randomly selected for the 2008 GA2LEN survey | 43.7 | 49.0 | Diagnosis defined by questionnaire | 13.8 | Moderate bias | ||||
| Marcon, 2013 [66] | Italy | Population-based, retrospective, multi-case–control study | ≈3 | 662 | 360 (54.4) | Mild asthma versus nonasthma control | Subjects randomly selected from the general population belonging to the Italian Study on Asthma in Young Adults cohort and to the Italian branch of the European Community Respiratory Health Survey cohort | 43.8 | 49.0 | Diagnosis defined by questionnaire and lung function tests | 22.4 | **** | * | 5 | ||
| Lu, 2013 [46] | Singapore | Population-based, retrospective, cross-sectional survey | 1 | 2809 | 106 (3.8) | Asthma versus nonasthma control | Adults randomly selected from the Singapore National Mental Health Survey | 20.0–59.0 | 38.2 | Self-report of a doctor's diagnosis | NA | Low bias | ||||
| Traister, 2013 [51] | USA | Retrospective, cohort study | ≈6 | 160 | 59 (36.9) | Asthma versus nonasthma control | Outpatients selected by random computer-generated sequence | 44.6 | 33.7 | Asthma diagnostic ICD-9 CM code: 493 and spirometry tests | 35.1 | *** § | ƒ | 3 | ||
| Patel, 2013 [45] | USA | Population-based, retrospective, cross-sectional survey | 8 | 22 172 | 2873 (13.0) | Asthma versus nonasthma control | Representative sample of civilian, non-institutionalised subjects of USA selected from the National Health and Nutrition Examination Survey | 46.7 | 48.1 | Self-report of a physician's diagnosis | NA | Moderate bias | ||||
| Iribarren, 2012 [52] | USA | Prospective, cohort study (comorbidities were assessed retrospectively) | 13 | 407 190 | 203 595 (50.0) | Asthma versus nonasthma control | Adults selected from the Kaiser Permanente Northern California healthcare plan | 44.6 | 34.0 | Medical records of hospitalisation with primary discharge code ICD-9 CM 493.00−493.99 or ≥1 secondary code for asthma with a principal ICD-9 code for acute asthma-related respiratory conditions, or outpatient or ED visits for asthma | 17.4 | *** § | ** | * ƒ | 6 | |
| Luyster, 2012 [44] | USA and UK | Retrospective, cross-sectional study | NA | 282 | 222 (78.7) | Nonsevere asthma and severe asthma versus nonasthma control | Participants selected from the retrospective multicentre Severe Asthma Research Program cohort study | 31.5 | 47.4 | Evaluation and classification according to the ATS definition of refractory asthma; diagnosis of severe asthma required continuous oral corticosteroid use or high-dose ICS use and ≥2 of the 7 minor criteria [67] | 0.0 | Moderate bias | ||||
| Cazzola, 2011 [6] | Italy | Population-based retrospective, cross-sectional study | 1 | 909 638 | 55 500 (6.1) | Asthma versus nonasthma control | Subjects selected from the Health Search Database of the Italian College of General Practitioners | >14.0 | 47.3 | Asthma diagnostic ICD-9 CM code: 493 | NA | Low bias | ||||
| Hakola, 2011 [53] | Finland | Prospective, cohort study (comorbidities were assessed retrospectively) | 1–4 | 64 951 | 2196 (3.4) | Persistent asthma versus nonasthma control | Finnish public sector employees selected from national registers | 44.1 | 20.0 | Physician's diagnosis confirmation by the Social Insurance Institution of Finland | 18.3 | *** § | * ƒ | 5 | ||
| Ng, 2007 [43] | Singapore | Population-based, retrospective, cross-sectional survey | 1 | 1092 | 61 (5.6) | Asthma versus nonasthma control | Older adults selected from the National Mental Health Survey of Elderly of Singapore | ≥60.0 | NA | Self-report of a doctor's diagnosis | NA | Low bias | ||||
| Adams, 2006 [42] | Australia | Population-based, retrospective, cross-sectional household telephone interview survey | 1 | 7443 | 834 (11.2) | Asthma versus nonasthma control | Adults selected from the Collaborative Health and Well-being Survey | ≥18.0 | 50.9 | Self-report of a doctor's diagnosis | NA | High bias | ||||
| Goodwin, 2003 [41] | USA | Retrospective, cross-sectional study | ≈2 | 998 | 176 (17.6) | Asthma versus nonasthma control | Primary care patients | 18.0–70.0 | 25.1 | Asthma diagnostic ICD-9 CM code: 493 of a primary-care physician's diagnosis | NA | Moderate bias | ||||
| Goodwin, 2003 [35] | Germany | Population-based, retrospective, cross-sectional, core survey | 1 | 4181 | 236 (5.6) | Nonsevere and severe asthma versus nonasthma control | Representative community sample of adults | 41.1 | 41.0 | Questionnaire and physician's diagnosis | NA | Moderate bias | ||||
Data are presented as n or n (%), unless otherwise stated. NOS: Newcastle–Ottawa Scale; JBI: Joanna Briggs Institute; NHS: National Health Service; ICD: International Statistical Classification of Diseases and Related Health Problems; OPCS: Office of Population Censuses and Surveys Classification of Interventions and Procedures; NA: not available; GINA: Global Initiative for Asthma; OMA: omalizumab; ICS: inhaled corticosteroids; LABA: long-acting β2-adrenoceptor agonists; CM: Clinical Modification; ATS: American Thoracic Society; ERS: European Respiratory Society; ED: emergency department. #: cohort studies could not be assigned a star for the outcome item “adequacy of follow-up of cohorts”, as outcomes of interest were all assessed retrospectively and there was no mention of losses; ¶: case–control studies could not be assigned a star for the exposure item “non-response rate”, as outcomes of interest were all assessed retrospectively; +: each of the eight items of the JBI tool was rated as “yes” (1 point) and “no” or “not applicable” (0 points). The score for each cross-sectional study was calculated on the proportion of “yes” responses for the possible maximum score and rated as high, moderate or low risk of bias according to the achieved score expressed as percentage (high bias: ≤49.0%; moderate bias: 50.0–69.0%; low bias ≥70.0%); §: no star could be assigned for the selection item “demonstration that outcome of interest was not present at start of study”, as outcomes of interest were already present at baseline; ƒ: no star could be assigned for the outcome item “was follow-up long enough for outcomes to occur”, as outcomes of interest were already present at baseline.