Bronchiectasis
Conditions
Keywords
nontuberculous mycobacteria, corticosteroids, macrolides, antibiotics
Brief summary
The purpose of this study is to provide patients and their physicians with greater understanding of the risks and benefits of commonly used therapies for treatment of non-CF bronchiectasis
Detailed description
Non-CF bronchiectasis is a chronic inflammatory lung disease that is closely linked to pulmonary NTM disease. Both are rare but rising in incidence and disproportionately affect the elderly and women. Therapy of non-CF bronchiectasis aims to reduce inflammation via either ICS-induced immunosuppression or antibiotic-associated immunomodulation and/or suppression of pathogenic organisms. Both strategies, pursued long-term alone or some cases concomitantly, have inherent risks, and the relative risks and benefits of these differential approaches are poorly studied to date. Ultimately, our study will provide patients and their physicians with greater understanding of the risks and benefits of these therapeutic choices.
Interventions
We will evaluate and compare the clinical effectiveness and safety of long-term inhaled corticosteroid and macrolide antimicrobial therapies
DRUGmacrolide therapy
We will evaluate and compare the clinical effectiveness and safety of long-term inhaled corticosteroid and macrolide antimicrobial therapies
Sponsors
Patient-Centered Outcomes Research Institute
University of Alabama at Birmingham
National Jewish Health
COPD Foundation
Oregon Health and Science University
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Within Medicare data, indicated diagnosis of Bronchiectasis by a Pulmonologist (ICD-9 code 494.0 and/or 494.1)
Exclusion criteria
* cystic fibrosis diagnosis, HIV infection, history of organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nontuberculous Mycobacterial (NTM) Disease | up to 8 years | Incidence of treated pulmonary nontuberculous mycobacterium (NTM) disease |
| Hospitalized Respiratory Infection | up to 8 years | Among a national cohort of non-CF bronchiectasis patients, we will compare the effectiveness of corticosteroid and macrolide therapy with regards to prevention of hospitalized respiratory infection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hip Fracture | up to 8 years | Hip fracture. |
| Opportunistic Infections | up to 8 years | Opportunistic infections. |
| All-cause Mortality | up to 8 years | All-cause mortality. |
| Sudden Cardiac Arrest | up to 8 years | Myocardial infarction event |
| Hemoptysis | up to 8 years | Hemoptysis event |
| Arrhythmia | up to 8 years | Arrhythmia (principal diagnosis) |
| All-cause Hospitalization | up to 8 years | All-cause hospitalization. |
| Sensorineural Hearing Loss | up to 8 years | Sensorineural hearing loss. |
Participant flow
Recruitment details
Complete national 2006-2014 Medicare data from Part A, B and D (but not C) were obtained from Center for Medicare and Medicaid Services for patients with ICD-9-CM code 494.0 or 494.1 (bronchiectasis without or with acute exacerbation).
Pre-assignment details
From the identified bronchiectasis cohort, we excluded patients with cystic fibrosis, HIV infection, or a history of organ transplant. Such patients are fundamentally different than non-CF bronchiectasis patients who lack these factors with regard to their risk for infection, hospitalization, and many of the outcomes under study in this proposal.
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Corticosteroids (ICS) New use was defined as the first prescription for a minimum 28 day (chronic) supply of ICS after a clean period of 12 months with no chronic use of either exposure of interest. ICS included ICS alone or in combination with long-acting beta agonists. | 83,589 |
| Macrolide Monotherapy New use was defined as the first prescription for a minimum 28 day (chronic) supply of macrolide monotherapy after a clean period of 12 months with no chronic use of either exposure of interest. Macrolide monotherapy was defined as oral azithromycin or erythromycin and no other chronic prescription within 30 days that could be associated with NTM therapy (ethambutol, a rifamycin, or a fluoroquinolone). Patients who did not start on macrolide monotherapy were excluded. | 6,500 |
| Total | 90,089 |
Baseline characteristics
| Characteristic | Inhaled Corticosteroids (ICS) | Macrolide Monotherapy | Total |
|---|---|---|---|
| Adapted Charlson comorbidity index (prior 12 months) 0 | 20514 Participants | 1534 Participants | 22048 Participants |
| Adapted Charlson comorbidity index (prior 12 months) 1 | 33959 Participants | 3119 Participants | 37078 Participants |
| Adapted Charlson comorbidity index (prior 12 months) 2+ | 29116 Participants | 1847 Participants | 30963 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 83589 Participants | 6500 Participants | 90089 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Comorbidities (any history) Allergic bronchopulmonary aspergillosis | 854 Participants | 64 Participants | 918 Participants |
| Comorbidities (any history) Alpha-1 antitrypsin deficiency | 292 Participants | 43 Participants | 335 Participants |
| Comorbidities (any history) Asthma | 33480 Participants | 1795 Participants | 35275 Participants |
| Comorbidities (any history) COPD/emphysema | 70548 Participants | 5050 Participants | 75598 Participants |
| Comorbidities (any history) Interstitial lung disease | 5526 Participants | 507 Participants | 6033 Participants |
| Comorbidities (any history) Lung cancer | 3497 Participants | 196 Participants | 3693 Participants |
| Comorbidities (any history) NTM History | 3164 Participants | 1307 Participants | 4471 Participants |
| Comorbidities (any history) Primary ciliary dyskinesia | 141 Participants | 23 Participants | 164 Participants |
| Comorbidities (any history) Primary immune deficiency | 3857 Participants | 466 Participants | 4323 Participants |
| Comorbidities (any history) Pseudomonas infection | 5123 Participants | 810 Participants | 5933 Participants |
| Comorbidities (any history) Silicosis | 103 Participants | 6 Participants | 109 Participants |
| Hospitalized respiratory infections in the 12 months prior to baseline | 9583 Participants | 885 Participants | 10468 Participants |
| Inpatient admissions in the 12 months prior to baseline 0 | 49795 Participants | 4108 Participants | 53903 Participants |
| Inpatient admissions in the 12 months prior to baseline 1 | 17943 Participants | 1299 Participants | 19242 Participants |
| Inpatient admissions in the 12 months prior to baseline 2+ | 15851 Participants | 1093 Participants | 16944 Participants |
| Number of acute respiratory infections in the 12 months prior to baseline 0 | 40746 Participants | 2478 Participants | 43224 Participants |
| Number of acute respiratory infections in the 12 months prior to baseline 1 | 20193 Participants | 1384 Participants | 21577 Participants |
| Number of acute respiratory infections in the 12 months prior to baseline 2-3 | 15993 Participants | 1499 Participants | 17492 Participants |
| Number of acute respiratory infections in the 12 months prior to baseline 4+ | 6657 Participants | 1139 Participants | 7796 Participants |
| Physician encounters in the 12 month prior to Baseline 0-7 | 24345 Participants | 1482 Participants | 25827 Participants |
| Physician encounters in the 12 month prior to Baseline 13-19 | 20549 Participants | 1771 Participants | 22320 Participants |
| Physician encounters in the 12 month prior to Baseline 20+ | 18668 Participants | 1721 Participants | 20389 Participants |
| Physician encounters in the 12 month prior to Baseline 8-12 | 20027 Participants | 1526 Participants | 21553 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 0 | 19013 Participants | 692 Participants | 19705 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 1 | 15157 Participants | 941 Participants | 16098 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 2 | 15437 Participants | 1032 Participants | 16469 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 3 | 11025 Participants | 1005 Participants | 12030 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 4 | 7232 Participants | 724 Participants | 7956 Participants |
| Pulmonologist encounters in the prior 12 months before baseline 5+ | 15725 Participants | 2106 Participants | 17831 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 362 Participants | 17 Participants | 379 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 3353 Participants | 160 Participants | 3513 Participants |
| Race/Ethnicity, Customized Black or African-American | 5338 Participants | 236 Participants | 5574 Participants |
| Race/Ethnicity, Customized Hispanic | 5188 Participants | 203 Participants | 5391 Participants |
| Race/Ethnicity, Customized Other/Unknown | 840 Participants | 64 Participants | 904 Participants |
| Race/Ethnicity, Customized White (non-Hispanic) | 68508 Participants | 5820 Participants | 74328 Participants |
| Region of Enrollment United States Midwest | 17129 Participants | 1612 Participants | 18741 Participants |
| Region of Enrollment United States Northeast | 18629 Participants | 992 Participants | 19621 Participants |
| Region of Enrollment United States South | 33289 Participants | 2897 Participants | 36186 Participants |
| Region of Enrollment United States West | 14542 Participants | 999 Participants | 15541 Participants |
| Residential category Metropolitan | 18328 Participants | 1702 Participants | 20030 Participants |
| Residential category Rural | 65261 Participants | 4798 Participants | 70059 Participants |
| Sex: Female, Male Female | 56583 Participants | 4750 Participants | 61333 Participants |
| Sex: Female, Male Male | 27006 Participants | 1750 Participants | 28756 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Hospitalized Respiratory Infection
Among a national cohort of non-CF bronchiectasis patients, we will compare the effectiveness of corticosteroid and macrolide therapy with regards to prevention of hospitalized respiratory infection.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Hospitalized Respiratory Infection | 4213 Events |
| Macrolide Monotherapy | Hospitalized Respiratory Infection | 317 Events |
p-value: <0.000195% CI: [1.23, 1.57]Regression, Cox
Primary
Nontuberculous Mycobacterial (NTM) Disease
Incidence of treated pulmonary nontuberculous mycobacterium (NTM) disease
Time frame: up to 8 years
Population: Analysis population excluded all patients with a history of NTM treatment or diagnosis prior to exposure start.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Nontuberculous Mycobacterial (NTM) Disease | 188 Events |
| Macrolide Monotherapy | Nontuberculous Mycobacterial (NTM) Disease | 32 Events |
Comparison: Due to the small sample size in the macrolide monotherapy group, for this outcome, the results are considered exploratory/descriptive only.p-value: 0.1995% CI: [0.51, 1.14]Regression, Cox
Secondary
All-cause Hospitalization
All-cause hospitalization.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | All-cause Hospitalization | 17939 Events |
| Macrolide Monotherapy | All-cause Hospitalization | 1352 Events |
p-value: <0.000195% CI: [1.08, 1.21]Regression, Cox
Secondary
All-cause Mortality
All-cause mortality.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | All-cause Mortality | 3362 Events |
| Macrolide Monotherapy | All-cause Mortality | 270 Events |
p-value: 0.295% CI: [0.96, 1.25]Regression, Cox
Secondary
Arrhythmia
Arrhythmia (principal diagnosis)
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Arrhythmia | 9508 events |
| Macrolide Monotherapy | Arrhythmia | 728 events |
p-value: 0.000595% CI: [1.07, 1.25]Regression, Cox
Secondary
Hemoptysis
Hemoptysis event
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Hemoptysis | 253 Events |
| Macrolide Monotherapy | Hemoptysis | 31 Events |
p-value: 0.9995% CI: [0.66, 1.51]Regression, Cox
Secondary
Hip Fracture
Hip fracture.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Hip Fracture | 919 Events |
| Macrolide Monotherapy | Hip Fracture | 77 Events |
p-value: 0.8795% CI: [0.8, 1.32]Regression, Cox
Secondary
Opportunistic Infections
Opportunistic infections.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Opportunistic Infections | 1585 Events |
| Macrolide Monotherapy | Opportunistic Infections | 180 Events |
p-value: 0.2395% CI: [0.76, 1.07]Regression, Cox
Secondary
Sensorineural Hearing Loss
Sensorineural hearing loss.
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Sensorineural Hearing Loss | 2574 Events |
| Macrolide Monotherapy | Sensorineural Hearing Loss | 347 Events |
p-value: <0.000195% CI: [0.64, 0.82]Regression, Cox
Secondary
Sudden Cardiac Arrest
Myocardial infarction event
Time frame: up to 8 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Sudden Cardiac Arrest | 892 Events |
| Macrolide Monotherapy | Sudden Cardiac Arrest | 81 Events |
p-value: 0.2195% CI: [0.67, 1.09]Regression, Cox