Patients with Nontuberculous Mycobacterial Lung Disease Exhibit Unique Body and Immune Phenotypes

Abstract

Rationale: Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. Objectives: To compare body morphotype, serum adipokine levels, and whole-blood cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM) with contemporary control subjects who are well matched demographically. Methods: We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar demographics. Body mass index and body fat were quantified. All patients with pNTM and a subset of control subjects were evaluated for scoliosis and pectus excavatum. Serum leptin and adiponectin were measured. Specific cytokines important to host-defense against mycobacteria were measured in whole blood before and after stimulation. Measurements and Main Results: Patients with pNTM and control subjects were well matched for age, gender, and race. Patients with pNTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis and pectus excavatum were significantly more prevalent in patients with pNTM. The normal relationships between the adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN-g and IL-10 levels were significantly suppressed in stimulated whole blood of patients with pNTM. Conclusions: This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined.Keywords: leptin; adiponectin; pectus excavatum; scoliosis; Marfan syndrome Chronic lung disease due to nontuberculous mycobacteria (NTM) is a growing public health concern (1-3). Recent studies estimate the incidence in the United States to be five to six cases per 100,000 and as high as 15.5 cases per 100,000 in persons over 50 years of age (3-5). Because the duration of symptomatic NTM lung disease is often years, the prevalence of disease is estimated to be 10 to 40 cases per 100,000 (1).In the United States, the most common NTM species associated with lung disease are Mycobacterium avium complex (MAC), Mycobacterium kansasii, and Mycobacterium abscessus. Although NTM are widespread in water and soil (6, 7), relatively few persons develop disease. Thus, intact immunity is likely pivotal for protection against NTM.Chronic lung disease is the most common form of NTM infection, manifested by two main radiographic patterns: (i) an upper lobe fibrocavitary pattern that occurs mostly in men with underlying lung disease such as chronic obstructive pulmonary disease (COPD) and (ii) a nodular-bronchiectasis pattern that often involves the right middle lobe and lingula and which appears to be more common in women with no clear risk factors (8)...

Changes in cholesterol level correlate with the course of pulmonary nontuberculous mycobacterial disease

“…The BMI of patients with PNTM disease was lower than that of age-, sex-and race-matched controls or uninfected healthy controls in previous studies (4,23,24). Ikegame et al reported that BMI at baseline is associated with disease spread in terms of the number of affected lung segments in PNTM disease (6).…”

“…Also, increased adiponectin decreases tumor necrosis factors and increases production of interleukin (IL)-10 and IL-1 receptor antagonist (IL1Ra). Katalija et al showed that immune-modulating adipokines were abnormally regulated in patients with PNTM disease (23). Several studies reported decreased cytokine production and interferon-γ secretion in patients with PNTM disease (28)(29)(30).…”

Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants

“…In addition, other phenotypic abnormalities occur at a higher frequency in these individuals than in the general population, including pectus deformity, scoliosis, mitral valve prolapse, high-arched palate, arachnodactyly, and hypermobility (1)(2)(3)(4)(5). These skeletal and cardiovascular manifestations are similar to phenotypic features noted in individuals with heritable connective tissue disorders such as Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome.…”

Lady Windermere syndrome

“…45 Other studies have also reported an increased incidence of scoliosis and pectus excavatum, occurring in up to 51% of patients with pulmonary NTM. 29,46 Mitral valve prolapse also occurs frequently in these patients. Many studies have shown that most women with LWS have a low-normal BMI and a slender body habitus with decreased subcutaneous fat.…”