Nontuberculous Mycobacterial Lung Disease Doubled the Risk of Death in a Managed Care Population

Nontuberculous mycobacterial lung disease (NTMLD) is known to be associated with increased mortality. Now, a new study examining the public health burden of NTMLD in the United States has found that all-cause mortality, adjusted for other factors, more than doubled with NTMLD compared with an age- and sex-matched control group.¹

Studies have suggested that 5-year all-cause mortality in patients diagnosed with NTMLD ranges from 28% to 40%. The prevalence of NTMLD as well as NTMLD-related mortality are rising, likely because the US population is aging. The current matched cohort study analyzed 2007-2016 data from Clinformatics Data Mart from Optum—a large national managed care insurance plan database containing aggregated health claims covering approximately 15-18 million fully covered members annually. The population in the database is geographically diverse, with data for plan members in all 50 states, and is representative of a commercially insured population. Medicare Advantage members are also included in the group in increasing numbers in recent years.

The study’s primary end point was all-cause mortality. Comorbid conditions and tobacco use present at baseline were identified from inpatient and outpatient medical claims. The Charlson comorbidity index (CCI) was used to characterize patients’ overall disease burden and adjust for these baseline patient characteristics. Patients with NTMLD were matched with a control group with no NTMLD ICD-9 or 10 codes; the control group was randomly selected from the general population and matched 3:1 to the NTMLD sample according to birth year, gender, and benefit coverage. Survival was compared after adjusting for demographic factors and baseline comorbidities.

Two thousand and five patients with NTMLD and 6014 controls were identified (mean age of patients and controls, 67 years; 66% female) and followed for 3.4 and 3.7 years, respectively. The NTMLD group had substantially higher proportions of patients with asthma (23.3% vs 3.5%), bronchiectasis (36.5% vs 0.1%), chronic obstructive pulmonary disease (52.0% vs 5.9%), arrhythmia (22.6% vs 6.5%), coronary artery disease (18.5% vs 6.6%), heart failure (11.9% vs 4.1%), and cancer (18.5% vs 5.0%).

The analysis showed:

• A doubling risk of all-cause mortality in the NTMLD versus control group (hazard ratio [HR], 2.06; 95% CI, 1.52-2.79; P <.001).
• Older age was a significant risk factor for mortality in patients with NTMLD. All-cause mortality significantly increased with each additional 10 years of age (HR, 1.62; 95% CI, 1.34-1.82; P <.001).
• The mortality rates in age groups differed between NTMLD and control groups. The NTMLD group had a markedly higher rate of mortality among younger-aged patients.
• Inhaled corticosteroids were significantly associated with increased mortality, independent of NTMLD and other comorbidities.
• Obesity was associated with lower all-cause mortality, which is in line with studies that found an association between underweight body mass index and poor survival in patients with Mycobacterium Avium Complex lung disease. (Obesity and overweight have been associated with a reduced risk of active tuberculosis, perhaps due to immunoprotective effects of the obesity hormone leptin. The majority of deaths in the current study were in the NTMLD cohort; therefore, the overall protective effect of obesity may have emerged, in part, due to mitigating effects of obesity with NTMLD.)

The researchers note that they lacked data to assess the mortality impact of race/ethnicity, and the impact of genetic susceptibility on mortality was beyond the scope of the current analysis. They also lacked information on mycobacterial species and/or antibiotic sensitivity, which could potentially impact mortality risk.

“The incremental risk of all-cause mortality in NTMLD compared with controls represents a critical unmet medical need and requires effective management of the disease,” they conclude.

Reference

Marras TK, Vinnard C, Zhang Q, et al. Relative risk of all-cause mortality in patients with nontuberculous mycobacterial lung disease in a US managed care population. Respir Med. 2018;145:80-88. doi: 10.1016/j.rmed.2018.10.022.