Diagnosis Of Nontuberculous Mycobacterial Lung Disease Research Articles

Eliciting Patient Insights on the Burden of Nontuberculous Mycobacterial Lung Disease (NTM-LD) and Healthcare Gaps in Germany Through Qualitative Semi-structured Interviews.

Nontuberculous mycobacterial lung disease (NTM-LD) is a rare but growing health concern, particularly affecting vulnerable patients with chronic lung conditions. Understanding the patients' perspective on their disease and treatment expectations can help to identify healthcare gaps and improve overall patient care. Therefore, the main objective of the survey study was the evaluation of patient insights on the burden of the disease and healthcare gaps. The study used an online survey as a pre-screener to facilitate recruitment followed by semi-structured qualitative interviews. The interviews were conducted by phone from April 2019 to February 2020 in German language. Only patients with a self-reported confirmed NTM-LD diagnosis, managed and insured in Germany were included in this study. In total, 20 semi-structured qualitative interviews were conducted. Most (85%) patients had at least one coexisting pulmonary condition with cystic fibrosis (CF, n = 9) being most common. Chronic cough, fatigue, and dyspnea were the most reported symptoms. Of all the symptoms reported, fatigue was perceived as the most burdensome and 85% of patients felt limited in their daily life. It took a median of 5months for patients to receive an accurate diagnosis of NTM-LD and that time was doubled when excluding patients with CF (range 0-480months). Ninety percent of interviewed patients (n = 18) received drug treatment for NTM-LD and most of them (n = 17) reported having experienced side effects from their treatment. Patients' expressed a particular need for more comprehensive and reliable patient-friendly information on NTM-LD and a better awareness of physicians as well. NTM-LD can considerably impair the lives of patients and their families and/or caregivers. A multidisciplinary approach and establishment of more widespread regional expert centers for NTM-LD management in Germany with well-structured referral and communication pathways accompanied by peer-to-peer support of patient advocacy groups are urgently needed.

Analysis of time for diagnosis of nontuberculous mycobacterial lung disease and its associated factors in a tuberculosis-designated hospital in Shanghai

Objective: To investigate the pathogenic characteristics, bacteriological diagnosis time and its associated factors among patients with nontuberculous mycobacterial (NTM) lung disease in a large tuberculosis-designated hospital in Shanghai from 2020 to 2021, in order to improve diagnosis efficiency and formulate precision treatment. Methods: On the basis of the Tuberculosis Database in Shanghai Pulmonary Hospital, NTM patients diagnosed by the Department of Tuberculosis between January 2020 and December 2021 were screened. Demographic, clinical and bacterial information were retrospectively collected. Chi-square test, paired-sample nonparametric test and logistic regression model were used to analyze the factors associated with the diagnosis time of NTM lung disease. Results: A total of 294 patients with bacteriologically confirmed NTM lung disease were included in this study, 147 males and 147 females with a median age of 61(46, 69) years. Of them, 227 (77.2%) patients had comorbidity of bronchiectasis. Species identification results showed that Mycobacterium Avium-Intracellulare Complex was the main pathogen of NTM lung disease (56.1%), followed by Mycobacterium kansasii (19.0%) and Mycobacterium abscessus (15.3%). Species such as Mycobacterium xenopi and Mycobacterium malmoense were rarely identified, accounting for a total proportion of only 3.1%. Positive culture rates for sputum, bronchoalveolar lavage fluid and puncture fluid were 87.4%, 80.3% and 61.5%, respectively. Paired-sample analysis showed that the positive rate of sputum culture was significantly higher than that of smear microscopy (87.1% vs. 48.4%, P<0.01), while no statistical difference was observed between sputum and bronchoalveolar lavage fluid on positive culture rate (78.7% vs. 77.3%, P>0.05). Patients with cough or expectoration were observed with 4.04-fold (95%CI 1.80-9.05) or 2.95-fold (95%CI 1.34-6.52) higher probability of positive sputum culture, compared to those without. Regarding bronchoalveolar lavage fluid, female or patients with bronchiectasis had a 2.82-fold (95%CI 1.16-6.88) or 2.38-fold (95%CI 1.01-5.63) higher probability to achieve a positive culture. The median time to diagnosis of NTM lung disease was 32 (interquartile range: 26-42) days. The results of multivariable analysis showed that patients with symptom of expectoration (aOR=0.48, 95%CI 0.29-0.80) needed a shorter diagnosis time in comparison with patients without expectoration. With Mycobacterium Avium-Intracellulare Complex as a reference, lung disease caused by Mycobacterium abscessus needed shorter diagnosis time (aOR=0.43, 95%CI 0.21-0.88), whereas those caused by rare NTM species were observed to require a longer diagnosis time (aOR=8.31, 95%CI 1.01-68.6). Conclusion: The main pathogen causing NTM lung disease in Shanghai was Mycobacterium Avium-Intracellulare Complex. Sex, clinical symptoms and bronchiectasis had an impact on the positive rate of mycobacterial culture. The majority of patients in study hospital were timely diagnosed. Clinical symptoms and NTM species were associated with the bacteriological diagnosis time of NTM lung disease.

1396. The Incremental Hospitalization Burden Associated with Nontuberculous Mycobacterial Lung Disease(NTMLD) among Patients with Chronic Obstructive Pulmonary Disease (COPD) in Japan

BackgroundNTMLD is a life-threatening pulmonary infection with increasing incidence and prevalence in Japan. It is associated with progressive lung damage and increased healthcare use. Many patients with NTMLD have comorbid respiratory conditions such as COPD. Treatment of NTMLD in patients with COPD is difficult, however there is limited data on the incremental burden that NTMLD adds to underlying COPD. We assessed the incremental burden associated with NTMLD in Japanese patients with COPD by comparing their hospitalizations to matched COPD patients without NTMLD.MethodsA retrospective cohort study was conducted using claims data provided by the Japan Medical Data Center (2015-2020). COPD patients with NTMLD were matched 1:3 to COPD patients without NTMLD (controls). Hospitalizations (all-cause, respiratory-related, and COPD-related) were accrued over a 1-year follow-up period after NTMLD diagnosis (index). Incremental burden of NTMLD was assessed by comparing hospitalizations between COPD patients with NTMLD and controls with univariate and multivariate analyses adjusting for comorbidities during 1-year pre-index period.ResultsA total of 492 COPD patients with NTMLD were matched by age and sex to 1476 controls. Mean (SD) age on index date was 56.6 (10.3) years and 61.4% were females. Compared to controls, NTMLD patients had higher prevalence of some pulmonary symptoms and comorbidities such as hemoptysis (11% vs 2%), dyspnea (1.6% vs 0.6%) and lung cancer (7% vs 4%). In univariate analyses, a higher percent of COPD patients with NTMLD had hospitalizations compared to controls (Fig 1A); the unadjusted annual hospitalization rates were also higher among patients with NTMLD (Fig 2A). Multivariate regressions after adjusting for pre-index comorbidities showed COPD patients with NTMLD were 1.9 times more likely to have an all-cause hospitalization, 2.8 times more likely to have a respiratory hospitalization, and 3.0 times more likely to have a COPD-related hospitalization (Fig 1B).ConclusionCOPD patients with NTMLD had a higher burden of hospitalization than COPD patients without NTMLD. The statistically significantly incremental burden associated with NTMLD in patients with COPD highlights the acute need for appropriate management of NTMLD in Japan. Disclosures Naoki Hasegawa, MD, PhD, Insmed Incorporated (Consultant, Scientific Research Study Investigator)Janssen Pharmaceuticals Inc (Consultant, Scientific Research Study Investigator) Kozo Morimoto, MD, Insmed Incorporated (Consultant) Ping Wang, PhD, Insmed Incorporated (Employee) Lu Zhang, PhD, Panalgo (Employee, Other Financial or Material Support, Lu Zhang is an employee of Panalgo which provides the analytic platform Instant Health Data that is used by Insmed) Mariam Hassan, PhD, B. Pharm, Insmed Incorporated (Employee) Anjan Chatterjee, MD, MPH, Insmed Incorporated (Employee)

Sputum Proteomics in Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacterial (NTM) infections are difficult to diagnose and treat. Biomarkers to identify patients with active infection or at risk of disease progression would have clinical utility. Sputum is the most frequently used matrix for the diagnosis of NTM lung disease. Can sputum proteomics be used to identify NTM-associated inflammatory profiles in sputum? Patients with NTM lung disease and a matched cohort of patients with COPD, bronchiectasis (BE), and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the United Kingdom. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, and CF), the presence of NTM lung disease defined according to American Thoracic Society/Infectious Diseases Society of America criteria, and severity of NTM. A subset of patients receiving guideline-concordant NTM treatment were studied to identify protein changes associated with treatment response. This study analyzed 95 sputum samples from 55 subjects (BE, n= 21; COPD, n= 19; CF, n= 15). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE, and CF found that 12 proteins were upregulated in CF compared with COPD, including MPO, AZU1, CTSG, CAT, and RNASE3, with 21 proteins downregulated, including SCGB1A1, IGFBP2, SFTPB, GC, and CFD. Across CF, BE, and COPD, NTM infection (n= 15) was not associated with statistically significant differences in sputum protein profiles compared with those without NTM. Two proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in the sputum protein profile. Patients with NTM and a decrease in immune response proteins had a subjective symptomatic improvement. Sputum proteomics identified candidate biomarkers of NTM severity and treatment response. However, underlying lung disease and typical bacterial pathogens such as P aeruginosa are also key determinants of the sputum proteomic profile.

PIN33 How Does Mortality Differ In Early Vs. Late Diagnosed Nontuberculous Mycobacterial Lung Disease Among Patients With Chronic Obstructive Pulmonary Disease (COPD)

Nontuberculous mycobacterial lung disease (NTMLD) is a rare lung disease that can add substantial incremental burden to respiratory diseases such as COPD. Symptom similarities with other respiratory diseases can lead to diagnostic delay of NTMLD and progressive lung damage. We sought to study associations between early versus late NTMLD diagnosis and mortality using a predictive model to identify time of probable NTMLD onset among COPD patients.

Chronic Pulmonary Aspergillosis Following Nontuberculous Mycobacterial Infections: An Emerging Disease.

Chronic pulmonary aspergillosis (CPA) following nontuberculous mycobacterial (NTM) lung disease is being increasingly recognized, especially in countries where tuberculosis is not endemic, with an incidence rate of 3.9–16.7%. NTM lung disease has been identified as a predictor of mortality in CPA patients. The major risk factors for NTM-associated CPA include fibrocavitary NTM lung disease, the presence of pulmonary emphysema, and high-dose corticosteroid use. The onset of CPA is 1.5–7 years following the diagnosis of NTM lung disease. The diagnosis can be made using standard criteria; however, serological diagnosis using Aspergillus precipitin has demonstrated a higher sensitivity and specificity when compared with fungal culture from respiratory specimens. Treatment is challenging since rifampicin and oral triazoles should not be used concomitantly. The prognosis is poor, and the factors associated with worse prognosis are corticosteroid use and high C-reactive protein level.

Is the Leicester Cough Questionnaire useful for nontuberculous mycobacterial lung disease?

Although the incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide, there is no established standard of care leading to eradication. Therefore, research on health-related quality of life (HRQOL) is important for patients with NTM-LD. HRQOL is commonly evaluated using the St. George's Respiratory Questionnaire (SGRQ), developed for chronic obstructive pulmonary disease (COPD). However, NTM-LD differs from COPD in that few patients complain of dyspnea or wheezing, and cough and sputum are their main symptoms. The Leicester Cough Questionnaire (LCQ) is an HRQOL questionnaire dedicated to cough, but few studies have used it for NTM-LD. This study evaluated HRQOL in patients with NTM-LD using the SGRQ and LCQ and clarified the usefulness of the LCQ. Information on age, height, weight, lung function, percent ideal body weight, laboratory data, radiological scores, exercise capacity, SGRQ, and LCQ were collected from the medical records of 81 patients. Correlations between SGRQ and LCQ domains were assessed using Spearman's rank correlation coefficients. Multivariate analysis was performed with SGRQ and LCQ total scores. Statistically significant correlations were observed between all domains, and the correlation between the total scores was -0.67 (p<0.01). Multivariate analysis with total scores as the dependent variable showed that the explanatory variables were lung function (p<0.05) and radiological score (p<0.05) in the SGRQ, and radiological score (p<0.05) and C-reactive protein level (p<0.05) in the LCQ. The LCQ, which evaluates an inflammatory response involved in the diagnosis of NTM-LD, may be useful to assess HRQOL in patients with NTM-LD.

Prognostic nutritional index as a predictor of mortality in nontuberculous mycobacterial lung disease.

BackgroundAlthough the association between nontuberculous mycobacterial lung disease (NTM-LD) and malnutrition is known, there are a few reports on the association between the nutritional score and death in patients with NTM-LD. This study investigated the association between the nutrition data at the time of NTM-LD diagnosis and death.MethodsA retrospective study was conducted for patients with NTM-LD who visited the Maebashi Red Cross Hospital from January 2014 to December 2018. The patients were divided into the survival and death groups and analyzed statistically.ResultsThe diagnostic criteria for NTM-LD were met by 150 patients. The median age was 70 years (range, 20–94 years). There were 51 (34.0%) men and 99 (66.0%) women. In the death group, the body mass index was significantly low, and there were significantly more patients with asthma. Further, computed tomography at the first visit revealed significantly fewer cases of the nodular bronchiectasis type. In the hematologic examination at the time of NTM-LD diagnosis, the white blood cell, neutrophil, and platelet counts and C-reactive protein and serum calcium levels were significantly higher in the death group, while the serum albumin level was significantly lower. In the death group, the prognostic nutritional index (PNI), calculated from the hematologic findings, was significantly lower, while the Glasgow Prognostic Score (GPS) was significantly higher. A logistic regression analysis was performed on items with significant differences, and the PNI and platelet count were independent factors predicting death.ConclusionsPNI might be effective as a prognostic factor for NTM-LD.

The clinical analysis of chronic obstructive pulmonary disease patients complicated with nontuberculous mycobacterial pulmonary disease

Objectives: Long-term use of inhaled corticosteroids (ICS) was reported as a risk factor for patients with chronic obstructive pulmonary disease (COPD) complicated with nontuberculous mycobacterial lung disease (NTM-LD). But it was not reported often in China. Methods: We conducted a retrospective analysis of patients who were diagnosed with COPD and NTM-LD in our department from January 1(st) 2017 to December 31(th) 2018. Results: This study consisted of 10 male and 5 female patients with a mean age of (66±7) years. The detailed clinical data and radiological images were reviewed systemically. There were 4 current smokers (26.7%) and 6 past smokers (40%). All cases were current ICS users, with a mean duration of (27.3±9.7) months, ranging from 3 months to 61 months. Among them, 8 cases (53.3%) used inhaled fluticasone and 7 cases (46.7%) used inhaled budesonide. Aggravated coughing (15 cases, 100%), expectoration (15 cases, 100%) and dyspnea (10 cases, 66.7%) were the common clinical manifestations, although fever was only reported in 4 cases (26.7%). All cases showed normal white blood cell count and lymphocyte count, and some of them (7 cases, 46.7%) showed elevated erythrocyte sedimentation rate and C-reactive protein. Most of them (14 cases, 93.3%) had normal TB-SPOT results. Multiple focal bronchiectasis (9 cases, 60%) and significant emphysema (12 cases, 80%) were the common manifestations of basic high-resolution CT (HRCT) prior NTM infection. The occurrence of bronchiectasis (15 cases, 100%), "tree in bud" sign (12 cases, 80%) and tiny cavities (8 cases, 53.3%) were the common HRCT abnormalities for the NTM-LD cases. According to the 2007's NTM-LD diagnosis criteria, most of them (13 cases, 86.7%) were diagnosed with positive sputum samples at least twice, and 2 cases were diagnosed with positive CT-directed bronchial alveolar lavage fluid. NTM-PCR analysis was performed routinely for the isolated NTM samples to identify the NTM species. Mycobacterium avium complex (MAC) was the most common NTM species (8 cases, 53.3%). After treatment with proposed anti-NTM strategies, most cases improved (9 cases, 60%), and some of them (4 cases, 26.7%) were cured and a few cases (2 cases, 13.3%) relapsed. Conclusions: When COPD patients treated with ICS showed aggravated cough, expectation and/or dyspnea, and new occurrence of bronchiectasis and/or "tree in bud" sign in the recent HRCT, the differential diagnosis of NTM-LD should be considered. Respiratory samples should be arranged for NTM cultures and PCR analysis as soon as possible. Earlier antimicrobial strategies according to the identified NTM species would improve the clinical outcomes.

Relative risk of all-cause mortality in patients with nontuberculous mycobacterial lung disease in a US managed care population.

The risk of all-cause mortality of nontuberculous mycobacterial lung disease (NTMLD) in the United States (US) population is not well established. This study aims to assess the public health burden of NTMLD in the US by comparing the relative risk of all-cause mortality in the NTMLD population with an age- and sex-matched cohort from the general population. Patients with physician claims for NTMLD (ICD-9 0.031; ICD-10 A31.0) were identified between 2007 and 2016 from a large US national managed care insurance plan covering approximately 15-18 million members annually. A control group with no NTMLD ICD-9 or 10 codes was randomly selected from the general population and matched 3:1 to the NTMLD sample according to birth year, gender, and insurance benefit coverage. The date of first NTMLD diagnosis of each patient was assigned to the matched controls as the index date. The Cox proportional hazard method compared survival between cohorts, adjusting for demographic factors and baseline comorbidities. A total of 2005 patients with NTMLD and 6014 controls were identified, with a mean follow-up duration of 3.4 years and 3.7 years, respectively. The NTMLD group had substantially higher proportions of patients with asthma (23.3% versus 3.5%), bronchiectasis (36.5% versus 0.1%), COPD (52.0% versus 5.9%), arrhythmia (22.6% versus 6.5%), coronary artery disease (18.5% versus 6.6%), heart failure (11.9% versus 4.1%), and cancer (18.5% versus 5.0%). The unadjusted rate of all-cause mortality from the index date was 20.7 per 1000 person-years in the NTMLD group vs 5.6 per 1000 person-years in the control group (rate ratio = 3.73; 95% CI: 2.93-4.75). Multivariable Cox regression, adjusted for the above variables as well as all other important baseline covariates, showed a doubling risk of all-cause mortality (hazard ratio [HR] = 2.06; CI: 1.52-2.79; P < 0.001) in the NTMLD vs control group. All-cause mortality, adjusted for other factors, more than doubled with NTMLD compared with an age-sex-matched control group in a large US national managed care insurance plan.

Health Care Utilization and Expenditures Following Diagnosis of Nontuberculous Mycobacterial Lung Disease in the United States.

Nontuberculous mycobacterial lung disease (NTMLD) is an important public health concern that has been increasing in prevalence. To (a) describe hospitalizations and health care expenditures among patients with newly diagnosed NTMLD and (b) estimate attributable hospitalizations and expenditures to NTMLD in the United States. In this matched cohort study, patients and controls were identified from a large U.S. national managed care insurance database containing aggregated health claims of up to 18 million fully covered members annually. NTMLD was defined based on diagnostic claims for NTMLD on ≥ 2 separate occasions ≥ 30 days apart between 2007 and 2016. Thirty-six months of continuous enrollment (12 months before and 24 months after the first diagnostic claim) was required. Health care utilization and standardized health care expenditures were summarized over 12 months before NTMLD diagnosis and for 2 subsequent years. The percentage of patients that were hospitalized in years 1 and 2 was evaluated using a generalized mixed effects model with adjustment for baseline hospitalizations, Charlson Comorbidity Index, and baseline diseases. A general estimating equation model was used to evaluate health care expenditures. There were 1,039 patients in the NTMLD cohort and 2,078 in the control cohort. NTMLD patients had a 55.0% risk of hospitalization in year 1 (95% CI = 45.4-64.3) and a 38.8% risk in year 2 (95% CI = 30.0-48.4). The adjusted risk of hospitalization was significantly higher in the NTMLD group compared with the control group in year 1 (OR = 4.64; 95% CI = 3.74-5.76; P < 0.001) and year 2 (OR = 2.26; 95% CI = 1.78-2.87; P < 0.001). Year 1 adjusted mean health care expenditures for the total NTMLD patient population were $72,475 (95% CI = $58,510-$86,440) and for the matched control population were $28,405 (95% CI = $8,859-$47,950), with a difference of $44,070 (95% CI = $27,132-$61,008; P < 0.001). Year 2 adjusted mean expenditures for the overall NTMLD patient group were $48,114 (95% CI = $31,722-$64,507) and for the matched control group were $28,990 (95% CI = $9,429-$48,552), with a difference of $19,124 (95% CI = $7,865-$30,383; P < 0.001). Patients with NTMLD have a significantly greater risk of hospitalization and higher total health care expenditures than matched control patients without NTMLD. This study was financially sponsored by Insmed. Marras reports fees from Insmed, Astra Zeneca, RedHill, and Horizon, all outside the current work. Mirsaeidi has nothing to disclose. Eagle, Q. Zhang, Chou, and Leuchars are employees of Insmed. R. Zhang is a contracted consultant at Insmed. The views expressed here are those of the authors and are not to be attributed to their respective affiliations.

Risk factors for the development of chronic pulmonary aspergillosis in patients with nontuberculous mycobacterial lung disease.

Nontuberculous mycobacterial lung disease (NTM-LD) is increasingly recognized as an important predisposing condition for the development of chronic pulmonary aspergillosis (CPA), but there are limited data on the risk factors for CPA development in NTM-LD patients. We reviewed the medical records of 566 patients who, at the time of diagnosis of NTM-LD, did not have CPA and who received ≥12 months of treatment for NTM-LD between January 2010 and June 2015. Of these patients, 41 (7.2%) developed CPA (NTM-CPA group), whereas the remaining 525 patients did not develop CPA (NTM group). The median time to the development of CPA was 18.0 months from treatment initiation for NTM-LD. The NTM-CPA group was older and had significantly higher proportions of males, current smokers, and patients with a low body mass index (<18.5 kg/m2), when compared to the NTM group. Moreover, the NTM-CPA group was more likely to have a history of tuberculosis and chronic obstructive lung disease and to have used inhaled or systemic steroids. In the NTM-CPA group, more than 40% of patients had Mycobacterium abscessus complex (MABC) as the cause of NTM-LD, and the fibrocavitary form of NTM-LD was the most common; both associations were higher than in the NTM group. Overall, 17 (3%) patients died, and the NTM-CPA group had a higher mortality rate than did the NTM group (19.5% vs. 1.7%, respectively; P<0.001). In a multivariable analysis, old age, male gender, low body mass index, chronic obstructive lung disease, systemic steroids, MABC as the etiologic organism, and the fibrocavitary form of NTM-LD remained significant predictors of development of CPA. In conclusion, CPA occurred in 7.2% of patients after initiation of treatment for NTM-LD, and some risk factors were associated with CPA development. Given the worse prognosis, early diagnosis and treatment of CPA are important in patients with NTM-LD.

Nontuberculous Mycobacterial Lung Disease: Current State of Knowledge and Future Directions

The main objectives of the two symposia were to raise awareness of nontuberculous mycobacterial lung disease (NTM-LD); evaluate the key microbiological and clinical aspects of the disease, including its association with other conditions, such as bronchiectasis and common coinfections; outline the current treatment and management strategies; and review data from clinical trials of new therapies and how these could shape future management strategies. Dr Chalmers, Dr Griffith, and Dr Haworth opened the symposia by introducing NTM-LD and providing a brief overview of the key topics. Dr Ringshausen focussed on the epidemiology, prevalence, and burden of NTM-LD, and briefly discussed pathophysiology. Dr van Ingen outlined the microbiological diagnosis of NTM-LD, in particular the importance of molecular identification and drug susceptibility testing (DST). Dr Aliberti introduced bronchiectasis, outlined the relationship between the two diseases, and discussed the clinical relevance of comorbid disease. Dr Aksamit addressed the assessment and management of co-isolated NTM and other respiratory pathogens. Dr Griffith and Dr Loebinger each summarised the current treatment and management strategies, and reviewed the latest research regarding new therapies and what this could mean for the future. Dr Koh closed the symposium by outlining the latest clinical research on the natural history of NTM-LD from a global perspective.

Rate of All-cause Hospitalization at Year 2 Between Treatment Groups Following Diagnosis of Nontuberculous Mycobacterial Lung Disease in the USA

BackgroundThe study compared rates of hospitalization between treatment groups in patients with nontuberculous mycobacterial lung disease (NTMLD) in a US national managed care claims database.MethodsPatient (N = 1039) pharmacy claims at year 1 following NTMLD diagnosis were classified into 3 treatment groups including triple combo (macrolide + ethambutol + rifamycin ± other drugs) (G1), other antibiotics used by physicians for NTMLD (G2), and no treatment (G3). Hospitalization rates at year 2 were compared between treatment groups using mixed effects logistic regression to adjust for patient characteristics and comorbidities measured by Charlson Comorbidity Index (CCI) during the 12 months prior to NTMLD diagnosis (baseline).ResultsMean age was 66, 66 and 73 years with 65%, 70% and 66% women in G1 (n = 353), G2 (n = 388) and G3 (n = 298) respectively. At baseline, there was no difference on CCI (CCI≈2) between treatment groups. However, comorbidity distribution differed prominently in asthma (22.1%, 26.3% and 11.4%), arrhythmia (19.3%, 19.3% and 27.2%), cystic fibrosis (0.8%, 4.6% and 0%), immune disorder (7.6%, 9% and 2.7%), pneumonia (49.0%, 41.8% and 32.6%), and tuberculosis (9.3%, 8.2% and 5.4%), and in immunosuppressant use (51%, 51.5% and 25.2%). Baseline hospitalization was 31.7% in G1, 33.0% in G2, and 25.8% in G3. At year 2, CCI stayed almost unchanged from the baseline scores (1.9 in G1, 2.0 in G2, and 1.9 in G3). Unadjusted hospitalization rates were 19.6%, 27.8% vs 20.8%, and adjusted rates were 44.5%, 56.1% and 47.8% in 3 groups respectively (Figure). G2 had a 60% increase in risk of hospitalization after adjustment (odds ratio (OR)=1.60, 95% CI: 1.11–2.29, P = 0.01) compared with G1 but no statistically significant difference compared with G3 (OR=1.40, P = 0.08). Cerebrovascular disease (OR=1.8, P < 0.02), COPD (OR=1.60, P < 0.01), cystic fibrosis (OR=5.85, P < 0.01), depression (OR=1.64, P < 0.05), and other lung disease (OR=1.42, P < 0.05) were associated with a higher risk of hospitalization at year 2 after NTMLD diagnosis.ConclusionWe observed a lower hospitalization rate in NTMLD patients receiving antibiotics that were concordant with first line ATS/IDSA guidelines recommendations in comparison with those who used other antibiotic regimens.Disclosures E. Chou, Insmed Incorporated: Employee, Salary; G. Eagle, Insmed Incorporated: Employee, Salary; R. Zhang, Insmed Incorporated: Consultant, Consulting fee; P. Wang, Insmed Incorporated: Employee, Salary; Q. Zhang, Insmed Incorporated: Employee, Salary

Healthcare Resource Utilization and Costs Following Diagnosis of Nontuberculous Mycobacterial Lung Disease in the USA

BackgroundDespite increasing awareness of nontuberculous mycobacterial lung disease (NTMLD), reports on the economic impact of healthcare resource utilization (HCRU) and costs are limited.MethodsThe national managed care insurance database was searched for physician claims for NTMLD (ICD9 031.0 or ICD10 A31.0) on ≥2 separate occasions ≥30 days apart between 2007 and 2016. A patient cohort (n = 1039) was selected by including those who were insured continuously over 36 months. A control group (n = 2078) was randomly selected from the plan members without NTMLD and matched 2:1 to the NTMLD sample by age and sex. The diagnosis date of NTMLD patient was assigned to the matched controls as the index date. HCRU and standardized costs were summarized over 12 months (baseline) before NTMLD diagnosis and 2 subsequent years.ResultsMean age was 68 years with 67% women. Charlson comorbidity score was 2.0 (±2.2) in NTMLD vs 0.5 (±1.3) in control. NTMLD patients had substantially more respiratory and other disorders compared with the control group (20.6% vs 3.5% asthma, 36.7% vs 0.3% bronchiectasis, 50% vs 6% ColoradoPD, 2% vs 0% cystic fibrosis, 41.6% vs 1.4% pneumonia, 7.8% vs 0% tuberculosis) and had greater immunosuppressant use (43.8% vs 11.9%). NTMLD vs control group had a 30.5% vs 6.0% rate of hospitalization at baseline, 35.1% vs 6.9% at year 1, and 23% vs 7.3% at year 2. Mean (median) total annual healthcare costs in NTMLD vs control were $35,145 ($15,493) vs $5,660 ($587) at baseline, $47,248 ($18,626) vs $6,692 ($745) at year 1, and $28,959 ($11,385) vs $7,184 ($819) at year 2. Medical costs were $26,626 ($11,701) vs $4,370 ($209) at baseline, $35,508 ($12,416) vs $5,248 (288) at year 1, and $20,036 ($6,715) vs $5,488 ($400) at year 2; pharmacy spending was $8,519 ($2,209) vs $1,290 ($21) at baseline, $11,739 ($3,957) vs $1,444 ($45) at year 1, and $8,923 ($2,418) vs $1,696 ($55) at year 2.ConclusionObserved HCRU and costs are substantially higher in NTMLD vs control group and increase from baseline to year 1 then decrease to year 2 in NTMLD but continue to rise in control group. The reversed U-shape of total costs in patients with NTMLD may reflect joint economic outcomes of disease, comorbidity, and management.Disclosures E. Chou, Insmed Incorporated: Employee, Salary; G. Eagle, Insmed Incorporated: Employee, Salary; R. Zhang, Insmed Incorporated: Consultant, Consulting fee; P. Wang, Insmed Incorporated: Employee, Salary; Q. Zhang, Insmed Incorporated: Employee, Salary

Non-tuberculous mycobacterial lung disease: diagnosis based on computed tomography of the chest

To elucidate the accuracy and inter-observer agreement of non-tuberculous mycobacterial lung disease (NTM-LD) diagnosis based on chest CT findings. Two chest radiologists and two pulmonologists interpreted chest CTs of 66 patients with NTM-LD, 33 with pulmonary tuberculosis and 33 with non-cystic fibrosis bronchiectasis. These observers selected one of these diagnoses for each case without knowing any clinical information except age and sex. Sensitivity and specificity were calculated according to degree of observer confidence. Inter-observer agreement was assessed using Fleiss' κ values. Multiple logistic regression was performed to elucidate which radiological features led to the correct diagnosis. The sensitivity of NTM-LD diagnosis was 56.4% (95% CI 47.9-64.7) and specificity 80.3% (73.1-86.0). The specificity of NTM-LD diagnosis increased with confidence: 44.4% (20.5-71.3) for possible, 77.4% (67.4-85.0) for probable, 95.2% (87.2-98.2) for definite (P < 0.001) diagnoses. Inter-observer agreement for NTM-LD diagnosis was moderate (κ = 0.453). Tree-in-bud pattern (adjusted odds ratio [aOR] 6.24, P < 0.001), consolidation (aOR 1.92, P = 0.036) and atelectasis (aOR 3.73, P < 0.001) were associated with correct NTM-LD diagnoses, whereas presence of pleural effusion (aOR 0.05, P < 0.001) led to false diagnoses. NTM-LD diagnosis based on chest CT findings is specific but not sensitive. • Diagnosis of NTM-LD based on radiological findings showed high specificity. • Sensitivity of NTM-LD diagnosis was around 50%. • Inter- observer agreement was moderate. • Identification of tree-in-bud pattern, consolidation and atelectasis led to correct diagnoses.

Clinical Investigation of Nontuberculous Mycobacterial Lung Disease in Japanese Patients with Rheumatoid Arthritis Receiving Biologic Therapy

To review patients with rheumatoid arthritis (RA) receiving biologic therapy following a diagnosis of nontuberculous mycobacterial (NTM) lung disease and to evaluate disease deterioration according to clinical and radiological features and anti-NTM therapy. We retrospectively analyzed medical records of 11 human immunodeficiency virus-negative patients with RA (median age, 64 years) receiving biologic therapy following diagnosis of NTM lung disease. NTM species included Mycobacterium avium complex in 9 patients (81.8%) and M. gordonae in 2 (18.2%). Underlying respiratory disease was present in 6 patients (54.5%), and most (81.8%) had radiographic features of nodular/bronchiectatic disease. Extent of NTM disease was 1-2 pulmonary lobes in 6 patients (54.5%), 3-4 lobes in 5 patients (45.5%), and 5-6 lobes in none. The results of radiological evaluations were unchanged or improved in 7 patients (63.6%) and worsened in 4 (36.4%). Radiological outcome was worse in patients with poor RA control despite their receiving biologic therapies for RA. Two of 3 patients receiving anti-NTM therapy as initial management for NTM improved, and 1 worsened. Three of 4 patients with worsened radiological outcome had high erythrocyte sedimentation rate (> 50 mm/h). Radiological deterioration was not observed in the majority of patients with RA receiving biologic therapy with NTM lung disease, and radiological outcome of pulmonary NTM was favorable in some patients undergoing anti-NTM therapy. Further studies focusing on disease deterioration according to biologic therapy received during NTM followup are warranted to determine appropriate treatment of RA patients with NTM lung disease.

Nutritional status and eating disorders: Neglected risks factor for nontuberculous mycobacterial lung disease?

Nontuberculous mycobacterial lung disease (NTMLD) in immunocompetent patients is an increasingly important epidemiologic concern. However, risk factors associated with susceptibility to NTMLD are not completely known. A prevalence of NTMLD appears to be rising, mainly in some populations such as middle-aged or elderly thin women, (a group including those with Lady Windermere syndrome) with neither remarkable history of respiratory disease nor smoking habit. Right middle lobe (RML) and lingula are often involved. Various predisposing factors and genetic defects have been described as possible causes of development of NTMLD, namely: voluntary suppression of cough, RML anatomical factors, menopause and mutations in cystic fibrosis transmembrane conductance regulator (CFTR). Malnutrition is also an important and common risk factor associated with other mycobacterial disease like tuberculosis (TB) and its probable association with NTMLD as have been pointed out for some authors. However, a real description of all nutritional aspects and eating habits of patients prior to NTMLD diagnosis is lacking. We hypothesized that malnutrition and eating disorders like anorexia nervosa could be risk factors that may promoting NTMLD. From a clinical viewpoint, if this hypothesis proves to be correct, eating habits and nutritional aspects should be taken into account in the diagnosis process of suspected NTMLD, since they are easily identifiable and treatable conditions.

Use of soluble triggering receptor expressed on myeloid cells-1 in non-tuberculous mycobacterial lung disease

Serum biomarkers are rarely studied in patients with non-tuberculous mycobacterial lung disease (NTM-LD). To investigate the role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory markers in NTM-LD. From April 2009 to March 2010, patients with NTM culture-positive respiratory specimens who were clinically and radiographically suspected of NTM-LD were evaluated for serum levels of sTREM-1, C-reactive protein, procalcitonin and interferon-gamma. Of the 86 patients enrolled, 60 fulfilled the diagnosis of NTM-LD. Using the receiver-operating characteristics curve analysis, serum sTREM-1 had the highest discriminative power for NTM-LD and colonisation (area under the curve = 0.714). Using a cut-off value of 180 pg/ml, the sensitivity and specificity of sTREM-1 were respectively 58% and 89%. Logistic regression analysis revealed that Mycobacterium avium complex, M. kansasii, positive sputum acid-fast smear and higher serum sTREM-1 level were independent risk factors for NTM-LD. Age >65 years and higher serum sTREM-1 level were associated with worse 6-month survival. In patients with respiratory specimens that are culture-positive for NTM with clinical suspicion of NTM-LD, serum sTREM-1 level measurements may be helpful in diagnosing and predicting outcome for NTM-LD.