Description of observational studies with respiratory infection as an outcome
| Primary author | McKeever23 | Qian24 | Ekbom25 | Kim26 | Lee27 | Brode28 |
| Year | 2013 | 2017 | 2019 | 2019 | 2013 | 2017 |
| Study design | Case-control | Cohort | Cohort | Cross-section | Case-control | Case-control |
| Length of study/follow-up | 90 days | Average of 4.8 years | Length of study: 2005–2010 | In several places mentions ’study period' but nowhere does it describe what that period was | Up to 3 years | 1 January 2001 to 31 December 2013 |
| Population | UK primary care patients in THIN (The Health Improvement Network) database | Pharmacy claims databases from 40% Quebec population and health databases of RAMQ (>7 million people) | Longitudinal Respiratory Health in Northern Europe (RHINE) Study | Total of 16 804 sites (43 tertiary general hospitals, 280 secondary general hospitals and 14 745 primary clinics) | HIRA database (Seoul, South Korea) | Registered residents of Ontario, Canada |
| Sample size | 6857 patients with asthma and pneumonia/LRTI, 36 312 control subjects | 152 412 subjects | 7284 in total, 587 with asthma | 831 613 | 427 cases have asthma and 2352 controls | 219 asthma cases and 872 controls |
| Age range | 18–80 years | 12–35 years | 28–54 years | 15 years + | 20 years+ | >66 years |
| Asthma diagnosis definition | GP records via NIH database | >1 prescription for a respiratory medication | Self-reported diagnosis or asthma-related symptoms | Treated with asthma medications or received inpatient care for asthma using insurance asthma codes | ICD-10 codes | Validated algorithms |
| ICS type (drug/name) | Beclomethasone, budesonide, fluticasone propionate, ciclesonide/ mometasone | Budesonide, fluticasone 'and others' | Fluticasone propionate, budesonide | No mention | Beclomethasone, budesonide, fluticasone, triamcinocline, ciclesonide, flunisolide | Beclomethasone, budesonide, ciclesonide, fluticasone propionate or momethasone |
| Control/comparison group | Asthma with no ICS in 90 days before index | No ICS ever in population using respiratory medication at least once | ICS not used, both people with and without asthma | Not using ICS during undefined study period | Asthma, no ICS | Asthma, no ICS |
| Primary outcome of study—LRTI or pneumonia | Pneumonia/LRTI recorded in GP database | Hospitalised pneumonia using hospital records | Hospitalised pneumonia from hospital records | Pneumonia using insurance pneumonia codes—not told where pneumonia was treated (primary or secondary care) | TB | NTM-PD |
| Secondary outcomes of study | N/A | N/A | N/A | N/A | N/A | TB |
| Statistical analysis | Conditional logistic regression | Quasi-cohort methodology | Poisson regression | Logistic regression | Conditional logistic regression | Conditional logistic regression |
| Adjusted covariates | Priori confounders, number of relievers in the past year, Charlson Comorbidity Index Score, smoking, social class and use of oral steroids in the past year | Age (matched by design), gender, severity of disease and other comorbidity associated with a risk of pneumonia. Use of NSAIDs, anti-depressants and narcotics | Age, BMI, smoking and centre | Age, sex, insurance type, hospital type, Charlson Comorbidity Index, hospitalisation, and ICS use | LAMA use, SABA use, SAMA use, OCS use, presence of TB sequelae, immunosuppressant use, other comorbidities (malignancy, diabetes, chronic renal failure/dialysis, silicosis, malabsorption, HIV/AIDS and transplantation), Charlson Comorbidity Index and healthcare usage | Income, rurality, aggregated diagnostic groups, comorbidities (bronchiectasis, chronic kidney disease, gastro-oesophageal reflux disease, HIV, interstitial lung disease, rheumatoid arthritis), prior TB, medication use, and surrogates of severity of OLD and exacerbations of OLD (medications for OLD (any inhaled β-agonist, inhaled anticholinergic, oral corticosteroid or methylxanthine), hospitalisation for OLD, spirometry, home oxygen use) |
| Crude results | Risk of pneumonia/LRTI: OR=1.46 for beclomethasone, OR=1.82 for budesonide, OR=0.95 for ciclesonide/mometasone, OR=2.71 for fluticasone propionate | Rate ratio (risk of pneumonia in ICS users with that in non-users): RR current users=2.59 | N/A | OR, 2.00; 95% CI 1.97 to 2.02 | OR=1.22 (0.96–1.55) | OR of NTM-PD with current ICS use=1.76 (1.23–2.51) |
| Adjusted results | Risk of pneumonia/LRTI: OR=1.09 for beclomethasone, OR=1.20 for budesonide, OR=0.71 for ciclesonide/mometasone, OR=1.64 for fluticasone propionate | Rate ratio (risk of pneumonia in ICS users with that in non-users): RR current users=1.83 | IRR of pneumonia: fluticasone 6 years=7.92 (2.32–27.0) No significant effect found with <6 years or with budesonide | OR=1.38; 95% CI 1.36 to 1.41 | Adjusted OR=1.46 (1.11–1.96) | Adjusted OR of NTM-PD with current ICS use=1.56 (0.93–2.62) |
BMI, body mass index; GP, general practitioner; HIRA, health insurance review and assessment; ICD-10, international classification of diseases 10th revision; ICS, inhaled corticosteroid; IRR, incidence rate ratio; LAMA, long-acting muscarinic antagonist; LRTI, lower respiratory tract infection; NIH, national institute of health; NSAID, non-steroidal anti-inflammatory drug; NTM-PD, non-tuberculous mycobacterial pulmonary disease; OCS, oral corticosteroids; OLD, obstructive lung disease; RAMQ, Régie de l'assurance maladie du Québec; RR, relative risk; SABA, short-acting beta agonist; SAMA, short-acting muscarinic antagonist; TB, tuberculosis.