Risk of pneumonia in asthma patients using inhaled corticosteroids: A quasi-cohort approach
Bibliographic record
Abstract
Background: Inhaled corticosteroids (ICS) are commonly prescribed to patients with persistent asthma as the first-line treatment. Studies of ICS have generally shown a good efficacy and safety profile. However, following the Towards a Revolution in COPD Health (TORCH) trial, several large observational studies were also able to link the use of ICS to excess pneumonia risk in Chronic Obstructive Pulmonary Disease (COPD) patients. The risk of pneumonia in asthma patients using ICS is nevertheless a contentious issue. Methods: We formed a new-user cohort of patients with asthma aged 12 to 35 treated from January 1st, 1990 to December 31st, 2007. Subjects were identified using the Quebec health insurance databases – Régie de l'assurance maladie du Québec (RAMQ) and followed through 2007 or until a pneumonia event, defined as first hospitalization with a diagnosis of pneumonia identified in the RAMQ hospitalization database, including deaths due to pneumonia. A quasi-cohort approach was used where all cases of pneumonia were identified and the quasi-cohort (controls) consisted of 10 person-days per case, selected by incidence density random sampling from all person-days of follow-up in the cohort. Subjects were considered currently exposed if they had an ICS prescription 60 days prior to their index person-moment. Secondary analyses were also done to investigate possible relationships of pneumonia onset and ICS doses, as well as types. A quasi-cohort approach with conditional logistic regression was then used to estimate the rate ratio (RR) and the rate differences (RD) of pneumonia associated with ICS use, adjusted for age, sex, asthma severity, and several related comorbidities. Sensitivity analyses were also performed to explore possible biases.Results: The study cohort included 152,412 patients, of which 1928 had a pneumonia event in the average of 4.1 years of follow up (incidence rate 3.1 per 1000 per year). Using the 1928 cases and 19,275 quasi-cohort person-days, current ICS use is associated with an 83% increase in the rate of pneumonia (RR 1.83; 95% CI 1.57 to 2.14), or an excess of 2.16 cases per 1000 person-years (RD 2.16; 95% CI 1.41 to 2.91). High doses of ICS (fluticasone equivalent dose: >500 μg/day) is associated with a 96% increase in rate of pneumonia (RR 1.96; 95% CI 1.64 to 2.34) or an excess of 2.42 cases per 1000 person-years (RD 2.42; 95% CI 1.52 to 3.33). The rate of pneumonia is also found to be higher in users of budesonide (RR 2.67; 95% CI 2.05 to 3.49 & RD 3.42; 95% CI 1.66 to 5.19) and fluticasone (RR 1.93; 95% CI 1.58 to 2.36 & RD 2.47; 95% CI 1.38 to 3.57) as compared to other classes of ICS (RR 1.23; 95% CI 0.92 to 1.63 & RD 1.16; 95% CI -0.19 to 2.51), which include beclomethasone, ciclesonide, and triamcinolone. Sensitivity analyses overall yield consistent results, except one which suggests potential protopathic bias through its decreased magnitude of risk (RR 1.48; 95% CI 1.22 to 2.78). Conclusions: ICS use in asthma patients is associated with an increased risk of pneumonia, particularly with high doses and with both budesonide and fluticasone. These findings require replication in view of the observed potential protopathic bias.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.031 | 0.027 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.004 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".