Results Summary
What was the research about?
Bronchiectasis is a health problem that damages the airways that carry air to the lungs. Patients with bronchiectasis are likely to get lung infections.
Two kinds of medicines can prevent lung infections. The first is steroids that patients take from an inhaler. The second is an antibiotic that patients take by mouth, called macrolide monotherapy. Patients with bronchiectasis may need to take these medicines long term, or for more than 28 days.
In this study, the research team looked at Medicare claims for patients with bronchiectasis who had a long-term prescription for antibiotics or steroids. The team compared patients’ risk of lung infections such as pneumonia and nontuberculous mycobacterium, or NTM. They also looked at other health problems from long-term use of these medicines.
What were the results?
Compared with patients who were prescribed antibiotics, patients who were prescribed steroids had a higher risk of
- A hospital stay for pneumonia or for any reason
- Outpatient treatment for lung infections
- Irregular heartbeat
However, they had a lower risk of hearing loss compared with patients who were prescribed antibiotics.
Patients who were prescribed steroids and those who were prescribed antibiotics had a similar risk of
- Getting an NTM infection
- Having a heart attack
- Breaking a hip
- Getting an infection due to a weakened immune system
- Staying in the hospital because they coughed up blood
- Dying
Who was in the study?
The study included Medicare claims for 90,089 adults treated for bronchiectasis; 83,589 were prescribed a steroid and 6,500 were prescribed an antibiotic. Of patients, 83 percent were white, 6 percent were black, 4 percent were Asian/Pacific Islander, and less than 1 percent were American Indian or Alaska native. Also, 6 percent were Hispanic. For 1 percent, race and ethnicity were unknown or other. The average age was 74, and 68 percent were women.
What did the research team do?
Using patient data from Medicare claims, the research team compared two groups. In the first, patients had a prescription for 28 days or more of steroids. In the second, patients had a prescription for 28 days or more of antibiotics. The team looked at the risk of lung infections or other health problems up to seven years after patients started the medicines. The team took into account other things, such as gender or other health problems, that might affect risk.
A group of patients with bronchiectasis provided input to the research team.
What were the limits of the study?
Most patients were over age 65; results may differ for younger patients. Medicare claims didn’t include information about patient’ symptoms or how sick they were. As a result, the research team couldn’t tell how well the medicines improved symptoms. Few patients had NTM infections, making it hard to detect differences between the two groups.
Future research could include younger patients and those with and without other lung problems.
How can people use the results?
Doctors and patients with bronchiectasis can use the results when considering treatments.
Professional Abstract
Objective
To compare the safety and effectiveness of long-term inhaled corticosteroid treatment with long-term oral macrolide monotherapy in preventing lung infections in patients with bronchiectasis
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | Medicare claims data from 90,089 adults treated for bronchiectasis |
| Interventions/ Comparators |
|
| Outcomes |
Primary: risk of pulmonary NTM disease and being hospitalized to treat pneumonia Secondary: risk of acute exacerbation, arrhythmia, myocardial infarction, sensorineural hearing loss, hip fracture, opportunistic infections, hospitalization for hemoptysis, hospitalizations for all other causes, all-cause mortality |
| Timeframe | Up to 7 years for primary outcomes |
This retrospective, observational cohort study compared the rates of lung infections and other adverse outcomes for long-term inhaled corticosteroid treatment versus long-term oral macrolide monotherapy for patients with bronchiectasis.
The study included Medicare claims data for 90,089 adults diagnosed with bronchiectasis by a pulmonologist. All patients received 28 days or more of a new prescription, with 83,589 receiving one for an inhaled corticosteroid and 6,500 receiving one for a macrolide antibiotic. Researchers compared the risk of pulmonary nontuberculous mycobacterial (NTM) disease, being hospitalized to treat pneumonia, and other study outcomes for the two treatment groups after adjusting for demographics, healthcare utilization, comorbidity, and clinical history variables.
Among patients, 83% were white, 6% were black, 6% were Hispanic, 4% were Asian/Pacific Islander, fewer than 1% were American Indian or Alaska native, and 1% were other or unknown race or ethnicity. The average age was 74, and 68% were female. Patients had no history of cystic fibrosis, HIV, or organ transplant.
An advisory panel of patients with bronchiectasis helped define outcomes and interpret results.
Results
Compared with patients who were prescribed macrolide monotherapy, patients who were prescribed inhaled corticosteroids had a higher risk of hospitalized pneumonia (adjusted hazard ratio [aHR]=1.39; 95% confidence interval [CI]: 1.23, 1.57), acute exacerbation of bronchiectasis (aHR=1.56; 95% CI: 1.49, 1.64), arrhythmia (aHR=1.15; 95% CI 1.06, 1.25), and all-cause hospitalization (aHR=1.15; 95% CI: 1.08, 1.12). However, patients who were prescribed inhaled corticosteroids had a lower risk of hearing loss (aHR=0.73; 95% CI: 0.64, 0.82).
The two treatments had similar risks of NTM disease, myocardial infarction, hip fracture, opportunistic infections, hospitalization for hemoptysis, and death.
Limitations
Most patients were over age 65; results may differ for younger patients. Because Medicare claims did not contain data on disease symptoms or severity, researchers could not assess how well each therapy treated bronchiectasis. Only a small number of patients had claims for NTM disease, making it difficult to detect differences between the treatments.
Conclusions and Relevance
In this study, when compared with macrolide monotherapy, inhaled corticosteroid treatment had a higher risk of hospitalized pneumonia, acute exacerbation of bronchiectasis, hospitalization, and arrhythmias, but a lower risk of hearing loss.
Future Research Needs
Future research could compare the safety and effectiveness of these treatments in younger patients and those with and without other lung diseases. Outcomes should include culture results for diagnosing NTM disease.
Final Research Report
View this project's final research report.
Journal Citations
Related Journal Citations
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- The reviewers wondered why the researchers revised the propensity scores (PS), calculated to account for differences in patient characteristics between intervention groups, to balance the treatment groups at 180 days after the start of treatment, rather than use the original PS at treatment start. The researchers explained that nontuberculous mycobacterium (NTM) infection can take a considerable amount of time to diagnose, so they felt that any incidences of NTM infection in the first six months were likely to be existing rather than new cases of disease. The researchers went on to explain that they recalculated PS because many things may have changed during those first six months that would affect the group balance established by the first PS calculations.
- The reviewers suggested that the report needed a conclusion section that more clearly interpreted options for patients and physicians, rather than provided a summary of findings. The researchers updated their conclusion section to characterize the strength of evidence from the study as well as the overall results. They stood by the conclusion that macrolide therapy was likely to be a better choice than chronic inhaled corticosteroids (ICS) for older bronchiectasis patients to avoid hospitalization for respiratory infections. However, they also acknowledged that the study results could not determine whether this was due to a benefit of macrolides or a risk of chronic ICS because they could not compare risk related to either of these drug classes to the risk related to not starting any new drug class.
- The reviewers commented that the report touts the involvement of patient advocacy organizations in the project but does not discuss the potential conflict of interest of an NTM advocacy organization receiving funding from pharmaceutical companies that may benefit from diagnosis and treatment of NTM. The researchers said they are very conscious of conflicts of interest and the need for transparency in research and noted that their project focused on two generic and widely available treatments. The researchers acknowledged that a partnership has recently been developed between drug developers and patient advocates for NTM disease, but said they saw this as a positive development, given lack of interest from federal funders or industry in the past.