Clinical relevance of pulmonary non-tuberculous mycobacterial isolates in three reference centres in Belgium : a multicentre retrospective analysis

Background/objectives: Assessing the clinical relevance of non-tuberculous mycobacteria (NTM) isolated from respiratory samples can be challenging. The epidemiology and pathogenicity of NTM species vary geographically. We aimed to outline the clinical relevance and associated radiological patterns of NTM species isolated in Belgium. Methods: We performed a retrospective multicentre analysis of all patients identified from the laboratory database with >= 1 respiratory sample growing NTM from January 2010 through December 2017. We collected clinical, radiological and microbiological data through medical record review and assessed clinical relevance according to ATS/IDSA criteria for NTM pulmonary disease (NTM-PD). Results: Of the 384 unique patients, 60% were male, 56% had a smoking history and 61% had pre-existing lung disease. Mycobacterium avium complex (MAC), M. gordonae and M. xenopi were the most frequently isolated species: 53, 15 and 8% respectively. 43% of patients met ATS/IDSA criteria, of whom 28% presented with fibrocavitary disease. Weight loss, fever, nodular bronchiectatic and fibrocavitary lesions on chest CT, and a positive acid-fast bacilli (AFB) stain were significantly associated with NTM-PD. The species with the highest pathogenic potential were M. abscessus (11/12), M. malmoense (6/7) and M. intracellulare (41/64). Conclusion: In our study, MAC was the most commonly isolated NTM species, but M. abscessus and M. malmoense showed the highest probability of being clinically relevant. Clinical relevance varied not only by species but also by radiological findings on chest CT and AFB staining. Clinicians should consider these elements in their treatment decision making. Prospective data including clinical outcome are needed to provide more robust evidence

Incidence and Risk Factors of Serious Adverse Events during Antituberculous Treatment in Rwanda: A Prospective Cohort Study

BACKGROUND: Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa. In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome. METHODS AND FINDINGS: Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009. Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28-40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm(3) (IQR 44-248 cells/mm(3)). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23). HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4-8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1-3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1-3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0-2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3-3.0). CONCLUSION: Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections

A BEAT-PCD consensus statement:a core outcome set for pulmonary disease interventions in primary ciliary dyskinesia

BACKGROUND: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD).METHODS: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts.RESULTS: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS.CONCLUSION: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.</p

Lack of Correlation of Sinonasal and Otologic Reported Symptoms With Objective Measurements Among Patients With Primary Ciliary Dyskinesia: An International Study.

peer reviewedSinonasal and otologic symptoms are common among patients with primary ciliary dyskinesia (PCD) of all ages. We used baseline data from the ENT Prospective International Cohort of PCD patients (EPIC-PCD), the first PCD cohort focused on ENT disease manifestations. We assessed agreement between patient- or parent-reported symptoms and relevant examination findings, and calculated unweighted Cohen’s kappa to adjust for agreement by chance. We included 404 participants, from 12 centres. We found no correlation between patient-reported sinonasal symptoms and relevant clinical examination findings. Otologic symptoms correlated poorly or weakly with otoscopy and audiometry findings, with age and centre identified as determinants of agreement

Bronchiectasis and asthma:Data from the European Bronchiectasis Registry (EMBARC)

Background: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.</p

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)

Background A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. Methods We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. Results 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV 1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22–1.38; p&lt;0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44–1.67; p&lt;0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52–2.39; p&lt;0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29–1.56; p&lt;0.0001), 1.98 (95% CI 1.77–2.21; p&lt;0.0001) and 3.05 (95% CI 2.25–4.14; p&lt;0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01–1.24; p=0.027), for each increment in sputum purulence. Conclusion Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.</p

Bronchiectasis and asthma:Data from the European Bronchiectasis Registry (EMBARC)

Background: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.</p

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients