Columbus, Ohio – October 1, 2015, Mac Tools is proud to announce the newly wrapped Mac Tools Top Fuel Dragster to bring awareness to Breast Cancer. Top Fuel driver, Doug Kalitta and crew will be wearing matching Breast Cancer Awareness crew shirts and will unveil the pink dragster proudly displaying our Wrenching for a Cure branding. Mac Tools is a proud supporter of The Stefanie Spielman Fund for Breast Cancer Research and the Breast Cancer Society of Canada and as a company we wish to support Breast Cancer Awareness.
Treatment reduces the symptoms of MAC disease and improves your quality of life. However, treating MAC is difficult for several reasons: MAC can easily become drug-resistant.
October is national Breast Cancer Awareness Month and the Kalitta team and race fans will be doing their part to raise funds for research in the race for the cure. The Mac Tools dragster will be running the Breast Cancer Awareness wrap in Reading, PA, Dallas, TX, and Las Vegas, NV. Through Mac Tools’ Wrenching for a Cure product line, our goal is to raise awareness for Breast Cancer Research and donate a portion of our proceeds to the cause. Mac Tools is proud to donate a portion of all sales from the BCA products during the month of October in honor of Breast Cancer Awareness, which is just another reason that Mac Tools is Great to Work With™. Press Release Assets: .
Results Fourteen of 1035 identified studies, comprising 17 data sets with data from a total of 9035 patients, were eligible. The pooled estimate of five-year all-cause mortality was 27% (95% CI 21.3–37.8%). A high degree of heterogeneity was observed (I 2 = 96%). The mortality in the data sets varied between 10 and 48%.
Studies predominantly including patients with cavitary disease or greater comorbidity reported a higher risk of death. Patients in Asian studies tended to have a lower mortality risk. Predictors of mortality consistent across studies included male sex, presence of comorbidities and advanced patient age.
Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria, present in soil and water sources. NTM are thought of as opportunistic pathogens, with disseminated NTM disease being seen in patients with systemic impaired immunity (e.g. Interest in NTM pulmonary disease (NTM-PD) is increasing due to its growing prevalence in non-HIV populations. It can occur in the context of lung disease caused by, for example, bronchiectasis, chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF), and also in people with apparently normal lungs ,. NTM-PD symptoms are nonspecific and variable; patients may present with both respiratory and systemic complaints, which may relate to underlying lung disease.
NTM-PD usually manifests radiologically with fibrocavitary or nodular/bronchiectatic forms. NTM-PD diagnosis is generally made when the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) diagnostic criteria are met.
MAC is considered to be the most common cause of NTM-PD. It comprises various mycobacterial species, including M. Intracellulare, M. Avium (which has four subspecies), and several other less frequently isolated species including M. Chimaera ,.
The decision to treat MAC infections depends on the patient’s health status and risk of disease progression. According to published recommendations, patients with nodular/bronchiectatic MAC disease should be offered a combination of macrolide (clarithromycin or azithromycin), rifampin or rifabutin, and ethambutol ,. In patients with fibrocavitary or severe nodular/bronchiectatic disease, addition of parenteral aminoglycosides may be considered. Many are, however, refractory to first-line therapy and do not achieve sustained culture conversion. Effective treatment choices for these people are few, essentially limited to intensification or modification of the first-line regimen or surgical resection of infected lung tissue.
MAC lung disease natural history and long-term outcomes are poorly documented, particularly at the population level. A retrospective chart review of patients from Oregon, USA with respiratory NTM isolates found that the median time to death was 3.6 (range 0–7.7) years for cases meeting ATS/IDSA diagnostic criteria and 3.7 (range 0.0–8.6) years for those who did not ( p = 0.63). Here, 55% of the cases and 61% of the non-cases died during the follow-up period (2007–2014), with no statistically significant difference in five-year mortality between cases and non-cases. A previous systematic review of reported treatment outcomes in patients with MAC lung disease, based on a pooled analysis of 28 studies carried out between 1977 and 2004, found overall mortality to be 17% (95% confidence interval CI 15–18%). However, this mainly included studies of short duration, and the calculated mortality rates did not account for different patient follow up-times within the studies.
Thus, it is not possible to draw firm conclusions regarding longer-term mortality from this report. Another recent systematic review sought to examine comorbidities, health-related quality of life and mortality associated with NTM disease in various patient populations.
Again, variable follow-up times in the included studies (30 days to over 10 years) limited the understanding of long-term mortality. Moreover, no differentiation was made between NTM-PD and NTM-non-PD, or different NTM species.
We therefore sought to systematically review the published literature for data on long-term mortality in patients with MAC lung disease, pool five-year mortality results to gain an estimate of overall five-year all-cause mortality in these patients, and explore study characteristics that may have contributed to variability in mortality reports or predict patient outcome. Data sources Database searches were carried out in Medline® and Embase®, using PubMed® and ProQuest Dialog™ search tools, respectively, with a cut-off of 1st August 2017, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
English language studies were selected. The search strategy applied to each database is described in the Additional file.
Duplicates, case reports, nonclinical and animal studies were excluded, as were conference abstracts, newspaper articles, notes, news, biography, conference reviews, errata and lectures. Study selection Relevant studies were independently selected by two reviewing authors (WH and RD), who screened the article title and abstract initially, and then went on to review the article full text as needed.
Studies were included if they reported five-year all-cause mortality in cohorts of patients with MAC lung disease, or NTM-PD cohorts where the majority of patients (≥75%) had MAC lung disease. No restrictions were made regarding study design, patient subpopulation, or data collection (prospective or retrospective). Studies with fewer than ten patients were excluded because of uncertainty about validity of the presented data and outcome in smaller studies. Data extraction The following data were extracted from the selected publications: five-year all-cause mortality, proportion of MAC-attributable deaths, factors predicting all-cause mortality, all-cause mortality in patients with fibrocavitary or nodular/bronchiectatic disease, and MAC-related mortality in patients with fibrocavitary or nodular/bronchiectatic disease. Statistical analysis Heterogeneity in reported mortality rates was quantified in terms of the Q- and I 2-statistics.
The Cure Drum Machine
The Q-statistic is based on the chi-squared test and assesses deviation between individual study effect and the pooled effect across studies. A large Q-value relative to its degree of freedom provides evidence of heterogeneity of the measured outcome (variation in outcome estimates beyond chance). The I 2-statistic describes the percentage of the variability in outcome estimates due to heterogeneity rather than sampling error (chance). Five-year mortality rates were pooled across the studies using a random-effects model. The analysis was performed using Review Manager (RevMan version 5.3.
Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014 software). The PubMed® search of Medline® returned 845 studies, and the ProQuest Dialog search (using Embase® and Medline® databases) returned 1311 studies. Following comparison of the results and de-duplication, 1035 publications remained.
This selection was screened by title, abstract content and full text if needed. Following the exclusion criteria stated in the Methods section, 14 studies comprising 17 data sets with data from 9035 patients remained for analysis. A flowchart depicting this selection process is shown in Fig. The identified studies and their key characteristics are listed in Table –. Among these 17 data sets, nine were retrospective medical chart review studies – , five were retrospective population registry analyses – and three were from prospective, randomised studies ,. Three studies included data from two cohorts of patients with MAC lung disease, and these are considered separately for the purposes of this analysis ,. The number of patients with MAC in the studies ranged from 45 to 5543.
Two studies examined patients with other NTM infections (with the data for the MAC subgroup considered for this analysis) , , and one investigated nodular/bronchiectatic MAC lung disease. Three studies focused on newly-diagnosed MAC lung disease ,. Two of the included studies covered NTM-PD, however the majority of the patients in these studies were diagnosed with MAC lung disease ,. Studies are ordered within categories by year of publication ATS/IDSA American Thoracic Society/Infectious Diseases Society of America, CI confidence interval, FC fibrocavitary disease, HRCT high resolution computed tomography, IQR interquartile range, MAC Mycobacterium avium complex, NB nodular/bronchiectatic disease, NR not reported, NTM nontuberculous mycobacterium, PD pulmonary disease, SD standard deviation aMortality data were provided for two differently treated cohorts of patients with MAC lung disease. BPulmonary parenchymal disease by chest radiograph, sputum or bronchial wash containing M. Intracellulare, physician’s opinion that M. Intracellulare caused the disease.
‡Disease fulfilled 2007 ATS/IDSA criteria. §This study included primarily patients with MAC lung disease (86%). ‖These data sets included primarily MAC lung disease patients (84% in full cohort, 89% of those meeting ATS/IDSA criteria data set 13, 78% of those not meeting ATS/IDSA criteria data set 14).
¶Sputum culture positive for MAC on at least two occasions separated by at least a week, radiographic changes compatible with mycobacterial pulmonary disease, and/or clinical evidence of such disease Mortality rates in the identified studies. The five-year all-cause mortality data from each study, including the ranges and pooled estimate, are shown in Fig. The mortality in the studies ranged from 10.0% (95% CI 21.5–58.4%) to 48.0% (95% CI 33.1–62.9%).
Pooling data from all 17 data sets using a random effects model, the overall estimate of five-year all-cause mortality was 27% (95% CI 21.3–33.0%). The I 2 statistic was 96% and the Q-statistic was 365.1, indicating a high level of study heterogeneity. This is also demonstrated in a funnel plot of data from the selected studies (Fig. The proportion of all MAC-attributable deaths was reported by nine studies, and these data are shown in Fig.
MAC-related five-year all-cause mortality varied between 5% and 42%. Predictors of all-cause mortality are listed in Table. Several factors appeared to be consistent across studies. These include male sex , –, , presence of comorbidities –, –, , and advanced patient age , –,.
Predictors of better outcome include surgical treatment and nodular or bronchiectatic disease. Data set Negative association with all-cause mortality Positive association with all-cause mortality Reference 1 Surgical treatment Yeager 1973 2 Male sex Age ≥ 70 years Presence of systemic and/or respiratory comorbidity FC disease BMI 40 mm/h Gochi 2015 8,9 Male sex Age ≥ 70 years Malignancy, including lung cancer BMI 1 lung zone Low initial body weight Research Committee of the British Thoracic Society 2002 16,17 Adding clarithromycin vs. Ciprofloxacin to rifampicin and ethambutol therapy regimen Jenkins 2008.
BMI body mass index, FC fibrocavitary disease, HIV human immunodeficiency virus, NB nodular bronchiectatic disease, NTM nontuberculous mycobacteria, NTM-PD nontuberculous mycobacterial pulmonary disease aFactors found to be significant by multivariate analysis are listed Two studies examined the relationship between nodular/bronchiectatic and fibrocavitary MAC lung disease and MAC-related mortality ,. Both found that patients with fibrocavitary disease had increased five-year MAC-related mortality compared with patients with nodular/bronchiectatic disease (Fig.
One study also analysed the relationship between radiologic types of MAC lung disease and all-cause five-year mortality. This demonstrated that patients with fibrocavitary disease have a substantially greater risk of death compared with nodular disease (Fig. Effect of study region on five-year mortality We performed a sensitivity analysis using the geographic region in which the selected studies were conducted (Additional file: Table S1). The analysis demonstrated that patients in Asian studies tended to have a lower five-year mortality (19, 95% CI 14–23%) compared with Europe (35, 95% CI 27–43%) and North America (33, 95% CI 32–35%). The studies identified in this systematic review show that, in general, patients with MAC lung disease are at a high risk of death following their diagnosis, with a pooled estimate of five-year all-cause mortality of 27%.
In line with previous reports , we found there to be considerable heterogeneity between studies, with an I 2 value of 96% and Q-statistic of 365.1. Several publications have demonstrated the incremental impact of NTM infection on patient mortality. Adjemian and colleagues found that US patients aged over 65 with NTM-PD within a nationally-representative sample were 40% more likely to die during the study period (1997–2007) than patients without NTM-PD. Recent work from Ontario, Canada, also reported an increased mortality in patients with MAC lung disease compared with a matched control group (HR = 1.57, 95% CI 1.48–1.66, P.