Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease

Szymanski, Eva P.; Leung, Janice M.; Fowler, Cynthia; Haney, Carissa; Hsu, Amy P.; Chen, Fei; Duggal, Priya; Oler, Andrew J.; McCormack, Ryan; Podack, Eckhard R.; Drummond, Rebecca A.; Lionakis, Michail S.; Browne, Sarah K.; Prevots, D. Rebecca; Knowles, Michael R.; Cutting, G.; Liu, Xinyue; Devine, Scott E.; Fraser, Claire M.; Tettelin, Hervé; Olivier, Kenneth N.; Holland, Steven M.

doi:10.1164/rccm.201502-0387oc

Cited by 133 publications

(109 citation statements)

References 48 publications

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“…In a recent study of genetic variation in patients with respiratory infection with nontuberculous mycobacteria and bronchiectasis, along with some family members without these organisms, ORIGINAL RESEARCH researchers reported results that are congruent with our hypothesis that genetic variants in heritable connective tissue disorders contribute to the development of bronchiectasis (49). Specifically, these 87 individuals (with and without mycobacteria) were exome sequenced, and data were filtered to include only genetic variants that had a population frequency less than 2% and the ability to affect protein structure.…”

Section: Discussionsupporting

confidence: 62%

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

Daniels¹,

Birchard

Lowe

et al. 2016

Annals ATS

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Rationale: Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders.Objectives: To determine whether lumbar dural sac size is increased in patients with idiopathic bronchiectasis as compared with control subjects, and to assess whether dural sac size is correlated with phenotypic characteristics seen in individuals with heritable connective tissue disorders.Methods: Two readers blinded to diagnosis measured anteriorposterior and transverse dural sac diameter using L1-L5 magnetic resonance images of 71 patients with idiopathic bronchiectasis, 72 control subjects without lung disease, 29 patients with cystic fibrosis, and 24 patients with Marfan syndrome. We compared groups by pairwise analysis of means, using Tukey's method to adjust for multiple comparisons. Dural sac diameter association with phenotypic and clinical features was also tested. Measurements and Main Results:The L1-L5 (average) anterior-posterior dural sac diameter of the idiopathic bronchiectasis group was larger than those of the control group (P , 0.001) and the cystic fibrosis group (P = 0.002). There was a strong correlation between increased dural sac size and the presence of pulmonary nontuberculous mycobacterial infection (P = 0.007) and long fingers (P = 0.003). A trend toward larger dural sac diameter was seen in those with scoliosis (P = 0.130) and those with a family history of idiopathic bronchiectasis (P = 0.149).Conclusions: Individuals with idiopathic bronchiectasis have an enlarged dural sac diameter, which is associated with pulmonary nontuberculous mycobacterial infection, long fingers, and family history of idiopathic bronchiectasis. These findings support our hypothesis that "idiopathic" bronchiectasis development reflects complex genetic variation in heritable connective tissue and associated transforming growth factorb-related pathway genes.Keywords: bronchiectasis; nontuberculous mycobacteria; heritable connective tissue disorders; dural sac diameter Correspondence and requests for reprints should be addressed to M.

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Section: Discussionsupporting

confidence: 62%

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

Daniels¹,

Birchard

Lowe

et al. 2016

Annals ATS

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“…They propose that MAC isolates should be speciated to better predict clinical disease and outcomes. In addition to differences observed in pulmonary disease based on pathogen characteristics, host factors affecting disease were also identified and reported by Szymanski and colleagues (26). They assessed genetic variations in individuals with NTM lung disease compared with healthy family members and a nonrelated control group, specifically looking at variants in the immune, cystic fibrosis transmembrane conductance regulator, cilia, and connective tissue gene sets.…”

Section: Nontuberculous Mycobacterial Lung Diseasementioning

confidence: 97%

Update in Tuberculosis/Pulmonary Infections 2015

Koenig

Furin

2016

Am J Respir Crit Care Med

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“…For NTM disease, a composite score would likely incorporate microbiological, chest imaging, and health-related quality-of-life measures. There is evidence that patients with pulmonary NTM have impaired mucociliary function and more lowfrequency variants in genes associated with immune, cystic fibrosis transmembrane conductance regulator, cilia, and connective tissue gene sets (28,29). In addition, there may be immunological markers that distinguish disease from airway colonization.…”

Section: Clinical Outcomes and Prognosis Develop A Composite Measure mentioning

confidence: 99%

Patient-Centered Research Priorities for Pulmonary Nontuberculous Mycobacteria (NTM) Infection. An NTM Research Consortium Workshop Report

et al. 2016

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Pulmonary Nontuberculous Mycobacterial Infection. A Multisystem, Multigenic Disease

Cited by 133 publications

References 48 publications

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

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

Update in Tuberculosis/Pulmonary Infections 2015

Patient-Centered Research Priorities for Pulmonary Nontuberculous Mycobacteria (NTM) Infection. An NTM Research Consortium Workshop Report

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