The Quiet Defenders: Immunoglobulin Levels As Predictors of Mortality in Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD)

Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic and challenging condition with rising global incidence. The 5-year all-cause mortality for NTM-PD ranges from 13-45%, particularly affecting vulnerable populations. Acquired immunoglobulin deficiency, which increases infection rates (17.2-21.7%) and associated mortality, is an area with limited data regarding NTM-PD mortality determinants. We conducted a retrospective cohort study to identify predictors of all-cause mortality in immunoglobulin-deficient patients with NTM-PD.

We retrospectively analyzed 512 NTM-PD patients diagnosed over a decade (2013–2023). Patients were identified via ICD-10 codes and validated through detailed medical record review, extracting 42 variables. The cohort was divided into immunoglobulin-deficient and non-deficient groups. The primary endpoint was all-cause mortality. Multivariate regression modeling, adjusting for confounders like age, sex, race, comorbidities, and treatments, was used to identify mortality risk factors.

Our analysis revealed a significant association between immunodeficiency and increased mortality (AOR: 3.56, 95% CI: 1.874-6.790, P=0.0001), indicating that immunoglobulin-deficient patients with NTM-PD had a 256% higher risk of death compared to those without immunodeficiency. Chronic Obstructive Pulmonary Disease (COPD) was another significant predictor of mortality (AOR: 1.91, 95% CI: 1.202-3.047, P=0.006), suggesting that patients with COPD had a 91% higher risk of mortality. Anemia also increased the mortality risk (AOR: 1.65, 95% CI: 1.052-2.542, P=0.029), indicating a 65% higher risk. Heart failure showed a borderline statistical significance (AOR: 1.64, 95% CI: 0.967-2.810, P=0.06), which implies a potential 64% higher risk of mortality, though this result was not conclusive.

The comorbidities that increase the risk of NTM-PD such as bronchiectasis (AOR: 1.07, 95% CI: 0.706-1.641, P=0.731), diabetes mellitus (AOR: 1.53, 95% CI: 0.851-2.716, P=0.155), chronic kidney disease (AOR: 1.44, 95% CI: 0.903-2.297, P=0.125), Obesity (AOR: 1.00, 95% CI: 0.999-1.090, P=0.63), and smoking status (AOR: 1.02, 95% CI: 0.633-1.663, P=0.916) were not statistically significant predictors.

Our study underscores the significant impact of immunoglobulin deficiencies in NTM-PD patients mortality outcome, highlighting the need for targeted management strategies. Immunoglobulin-deficient patients exhibit a markedly higher mortality risk, and addressing these immunological deficiencies could improve outcomes in this population. COPD and anemia were also critical predictors of mortality. The findings suggest that comprehensive management approaches, particularly in patients with these comorbidities, are essential. Further research with larger sample sizes is warranted to validate these findings and develop effective treatment strategies for improving outcomes in NTM-PD patients.