Int J Infect Dis. 2013 Nov;17(11):e1000-4.

Non-tuberculous mycobacterial disease is common in patients with non-cystic fibrosis bronchiectasis.

Mirsaeidi M, Hadid W, Ericsoussi B, Rodgers D, Sadikot RT.

Department of Veterans Affairs, Jesse Brown VA Hospital, Chicago, Illinois, USA; Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois at Chicago, 840 South Wood Street, M/C 719, Chicago, IL 60612, USA.

 

ABSTRACT:

Background: Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms. Cystic fibrosis (CF) patients are susceptible to NTM, but data about NTM in patients with non-CF bronchiectasis are limited. Methods: We conducted a retrospective, descriptive study at the University of Illinois Medical Center. All patients diagnosed with bronchiectasis (code 494) using the International Classification of Diseases, ninth revision (ICD-9), between 1999 and 2006, were identified. Clinical data including lung function, radiology studies, and presence of NTM in sputum were abstracted for those who met the study criteria. Results: One hundred eighty-two patients were enrolled in the study. Patients were divided into two groups: bronchiectasis with NTM isolates (n = 68) and bronchiectasis without isolates (n =114), and compared for clinical characteristics and underlying diseases. Mycobacterium avium complex (MAC) was the most common isolate. Fifty-five patients (30%) met the American Thoracic Society criteria for diagnosis of NTM disease. Gram-negative rods were commonly co-isolated. The probability of NTM isolation was significantly higher in elderly female patients (p = 0.04). Moreover, the probability of NTM isolation was significantly higher in the female group with low body mass index (BMI) (p = 0.002). Conclusions: NTM infections are common in non-CF bronchiectasis. MAC is the most frequently isolated NTM in these patients. There is also great variability in age and sex characteristics for NTM in non-CF bronchiectasis patients. Female patients with a low BMI are a high risk group for NTM infection in non-CF bronchiectasis. Routine screening for NTM is strongly recommended in this patient population.

Published by Elsevier Ltd.

KEYWORDS: BMI, Bronchiectasis, NTM, Non-CF, Non-tuberculous mycobacterial diseases

PMID: 23683809

 

SUPPLEMENT:

Bronchiectasis represents a significant disease entity that has been historically under-represented in medical literature (1). It is primarily a disease of the bronchi and bronchioles involving a vicious circle of infection and inflammation. Bronchiectasis in general can manifest in one of two forms: as a local or focal obstructive process of a segment or lobe of a lung or as a diffuse process involving most of the lungs (2). When extensive it has the potential to cause devastating illness by predisposing susceptible individuals to recurrent respiratory infections. While the lower respiratory tract is normally sterile, conditions such as bronchiectasis enable colonization of a variety of microbes.

Recently, the incidence of NTM infections has been increasingly reported both in the immunocompromised and immunocompetent population. NTM pulmonary infection associated with bronchiectasis is increasing worldwide (3). The numbers of patients who die from nontuberculosis mycobacteria are increasing in the US (4).

The diagnosis of NTM pulmonary infection is often delayed because symptoms are mild and excretion of NTM in sputum is intermittent with few colonies retrievable in culture. Many patients therefore require bronchoscopic examination or lung biopsy for diagnosis of NTM pulmonary disease (5). Hence, there is limited information about characteristics of dual diseases of NTM and bronchestasis, we therefore investigated a cohort of patients with adult-onset bronchiectasis to determine the prevalence of NTM in this group. Clinical indices were also compared with patients with bronchiectasis who did not grow NTM over that time, to determine whether there was any association with disease severity, antibiotic usage, radiographical changes or microbiology.

The study was performed at the University of Illinois at Chicago. A retrospective, chart review, was conducted after obtaining an approval from the Internal Review Board (IRB). All patients diagnosed with Bronchiectasis using an ICD code (494) were identified between 1999 and 2006. A list of 306 patients with an ICD code 494 was generated. Patients were included in the study if they were 18 years and older and had confirmed radiological changes suggestive of bronchiectsis (chest X-ray or CT scan of the chest) reported by radiologist which was independently evaluated by two clinicians (Figure 1). Patients with cystic fibrosis were excluded (n=6). Demographic, clinical and laboratory data were collected.

Categorical variables were described as counts and percentages or examined as predictors using odds ratio and were tested by the χ2 or, if applicable, exact tests. Univariate analysis was used to compare differences in demographic and clinical variables between bronchiectasis patient whom NTM isolated and non-NTM patients. Continuous variables were compared using Student t test for normally distributed variables and Wilcoxon rank-sum test for non-normally distributed variables.

In order to examine risk factors for NTM isolation, a stepwise logistic regression model was used. The outcome variable was isolation of NTM from respiratory secretions (sputum or BAL) and other variables listed in Table 1, which were statistically significant upon univariate analysis ( P <0.10) or considered clinically relevant.

The Kaplan–Meier estimate curve was used to determine the cumulative probability of NTM isolation for age and BMI in each gender; curves between the two groups were compared using the log-rank test. All data analyses were performed using SPSS software for Windows, version 17.0 (SPSS), two-tailed P-values were used and P values <0.05 were considered to be statistically significant.

A hundred and eighty two patients diagnosed with non-CF bronchiectasis were included. Table 1 shows the demographic, clinical and outcome characteristics of the study population. Mean age (SD) of patients with diagnosis of bronchiectasis was 64.5 (15.1) years. From the 182 patients who were identified with a diagnosis of bronchiectasis within this time frame, NTM was isolated from sputum or BAL in 68 (37%) patients. Mycobactrium avium complex (MAC) was isolated from 55 (81%), M.Chelonae 5 (7%), M. Kansassi 2 (3%), and other NTM were isolated from 6 (9%) patients. The diagnosis of bronchiectasis and isolation of NTM was significantly higher in female patients. This was further confirmed by logistic regression analysis (Table 2). Patients in whom NTM was isolated also gave a significant history of previous childhood infections (Table 2).

The mean (SD) of diagnosis delay per months was 44.95 (56.2). Gram-negative rods (entrobacteriace group and Pseudomona arouginosa bacilli) were isolated from 22 patients (14%) of whom 17 (77%) never been co-isolated NTM (p=0.031). 41 (23%) patients were hospitalized secondary to complications from bronchiectasis of whom 7 (10.3%) patients were those with NTM (p=0.002). Table 2 shows multivariate model, which accounted for the possible confounding effect of several factors, for patients with bronchiectasis with and without NTM.

The univariate analysis suggested that patient with bronchiectasis and NTM used clearance devices more frequently although there was no difference in the rate of usage of antibiotics for respiratory infections. Overall seven patients with bronchiectasis during this period underwent surgery, 2 of who had NTM isolated and 5 patients were from Non NTM group. 55 (30%) patients met the ATS criteria for the diagnosis of NTM disease.

The probability of NTM isolation was significantly higher in elderly female patients with non-CF bronchiectasis (p = 0.04), as shown in Figure 2. Moreover, The probability of NTM isolation was significantly higher in female group with low BMI (P=0.002), as shown in Figure 3.

In summary, this study shows that NTM is commonly isolated from patients with non-CF bronchietasis. The frequency of NTM in our bronchiectatic population was 37% of whom 30% met the ATS criteria for NTM disease definition. Additionally MAC appears to be the most common pulmonary NTM (88%) in this group. The current study also shows that elderly females and patients with low BMI are at a higher risk for acquiring NTM diseases. A better understanding of the role of NTM in the outcomes of patients with bronchiectasis may generate new therapeutic modalities for patients with severe disease. Furthermore, during the initial assessment of patients with bronchiectasis, physicians might need to consider sputum culture, and possibly bronchoscopy if lung imaging study is suggestive for NTM as a predictive factor for clinical outcomes.

Table 1 Demographic, clinical, and outcome characteristics for patients with bronchiectasis with and without NTM.

Legend for table 1: Data are no. (%) of patients, unless otherwise indicated.*Fisher test

 

Table 2. Logistic regression analysis results for patients with bronchiectasis with and without NTM.

Legend for table 2: Adjusted risk of NTM isolation in patients with Non-Cystic Fibrosis bronchiectasis by: Age> 65 years old, Male gender, Recurrent childhood pulmonary infections, History of previous IV-Antibiotic therapy, P > 0.05 by Hosmer and Lemeshow goodness-of-fit test.

 

 

References:

1. Smith MP. Non-cystic fibrosis bronchiectasis. J R Coll Physicians Edinb 2011; 41: 132-139; quiz 139.
2. Barker AF. Bronchiectasis. N Engl J Med 2002; 346: 1383-1393.
3. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association. Am J Respir Crit Care Med 1997; 156: S1-25.
4. Mehdi Mirsaeidi RFM, Joe G.N. Garcia, Dean E. Schraufnagel. Nontuberculous Mycobacterial Disease Mortality in the United States, 1999–2010: A Population-Based Comparative Study. PloS one 2014.
5. Huang JH, Kao PN, Adi V, Ruoss SJ. Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease: diagnostic and management limitations. Chest 1999; 115: 1033-1040.

Microsoft Word - Figure 1.docxFigure 1. The flowchart of study of Non-tuberculous mycobacterial disease in patients with Non-Cystic Fibrosis bronchiectasis

 Microsoft Word - Figure 2.docxFigure 2. The Age function stratified for sex and Non-tuberculous mycobacterial disease in patients with Non-Cystic Fibrosis bronchiectasis

Microsoft Word - Figure 3.docx Figure 3. The BMI function stratified for sex and Non-tuberculous mycobacterial disease in patients with Non-Cystic Fibrosis bronchiectasis

Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann