European Respiratory Society statement on airway clearance techniques in adults with bronchiectasis.

Airway clearance techniques (ACTs) are part of the main management strategy for patients with bronchiectasis. Despite being a priority for patients, accessibility, implementation and reporting of ACTs are variable in clinical settings and research studies. This European Respiratory Society statement summarises current knowledge about ACTs in adults with bronchiectasis and makes recommendations to improve the future evidence base. A task force of 14 experts and two patient representatives (10 countries) determined the scope of this statement through consensus and defined six questions. The questions were answered based on systematic searches of the literature. The statement provides a comprehensive review of the physiological rationale for ACTs in adults with bronchiectasis, and the mechanisms of action along with the advantages and disadvantages of each ACT. Evidence on ACTs in clinical practice indicates that the most frequently used techniques are active cycle of breathing techniques, positive expiratory pressure devices and gravity-assisted drainage, although there is limited evidence on the type of ACTs used in specific countries. A review of 30 randomised trials for the effectiveness of ACTs shows that these interventions increase sputum clearance during or after treatment, reduce the impact of cough and the risk of exacerbations, and improve health-related quality of life. Furthermore, strategies for reducing the risk of bias in future studies are proposed. Finally, an exploration of patients' perceptions, barriers and enablers related to this treatment is also included to facilitate implementation and adherence to ACTs.

Determining the most accurate 16S rRNA hypervariable region for taxonomic identification from respiratory samples.

16S rRNA gene profiling, which contains nine hypervariable regions (V1-V9), is the gold standard for identifying taxonomic units by high-throughput sequencing. Microbiome studies combine two or more region sequences (usually V3-V4) to increase the resolving power for identifying bacterial taxa. We compare the resolving powers of V1-V2, V3-V4, V5-V7, and V7-V9 to improve microbiome analyses in sputum samples from patients with chronic respiratory diseases. DNA were isolated from 33 human sputum samples, and libraries were created using a QIASeq screening panel intended for Illumina platforms (16S/ITS; Qiagen Hilden, Germany). The analysis included a mock community as a microbial standard control (ZymoBIOMICS). We used the Deblur algorithm to identify bacterial amplicon sequence variants (ASVs) at the genus level. Alpha diversity was significantly higher for V1-V2, V3-V4, and V5-V7 compared with V7-V9, and significant compositional dissimilarities in the V1-V2 and V7-V9 analyses versus the V3-V4 and V5-V7 analyses. A cladogram confirmed these compositional differences, with the latter two being very similar in composition. The combined hypervariable regions showed significant differences when discriminating between the relative abundances of bacterial genera. The area under the curve revealed that V1-V2 had the highest resolving power for accurately identifying respiratory bacterial taxa from sputum samples. Our study confirms that 16S rRNA hypervariable regions provide significant differences for taxonomic identification in sputum. Comparing the taxa of microbial community standard control with the taxa samples, V1-V2 combination exhibits the most sensitivity and specificity. Thus, while third generation full-length 16S rRNA sequencing platforms become more available, the V1-V2 hypervariable regions can be used for taxonomic identification in sputum.

Respiratory Physiotherapy and Bronchiectasis / Fisioterapia respiratoria y bronquiectasias

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Respiratory Muscle Training in Patients with Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis.

Background: Effective treatments for obstructive sleep apnoea (OSA) include positive pressure, weight loss, oral appliances, surgery, and exercise. Although the involvement of the respiratory muscles in OSA is evident, the effect of training them to improve clinical outcomes is not clear. We aimed to determine the effects of respiratory muscle training in patients with OSA. Methods: A systematic review was conducted in seven databases. Studies that applied respiratory muscle training in OSA patients were reviewed. Two independent reviewers analysed the studies, extracted the data and assessed the quality of evidence. Results: Of the 405 reports returned by the initial search, eight articles reporting on 210 patients were included in the data synthesis. Seven included inspiratory muscle training (IMT), and one included expiratory muscle training (EMT). Regarding IMT, we found significant improvement in Epworth sleepiness scale in −4.45 points (95%CI −7.64 to −1.27 points, p = 0.006), in Pittsburgh sleep quality index of −2.79 points (95%CI −4.19 to −1.39 points, p < 0.0001), and maximum inspiratory pressure of −29.56 cmH2O (95%CI −53.14 to −5.98 cmH2O, p = 0.01). However, the apnoea/hypopnea index and physical capacity did not show changes. We did not perform a meta-analysis of EMT due to insufficient studies. Conclusion: IMT improves sleepiness, sleep quality and inspiratory strength in patients with OSA.

Resistance mechanisms and molecular epidemiology of Pseudomonas aeruginosa strains from patients with bronchiectasis.

BACKGROUND: Non-cystic fibrosis bronchiectasis (BE) is a chronic structural lung condition that facilitates chronic colonization by different microorganisms and courses with recurrent respiratory infections and frequent exacerbations. One of the main pathogens involved in BE is Pseudomonas aeruginosa. OBJECTIVES: To determine the molecular mechanisms of resistance and the molecular epidemiology of P. aeruginosa strains isolated from patients with BE. METHODS: A total of 43 strains of P. aeruginosa were isolated from the sputum of BE patients. Susceptibility to the following antimicrobials was analysed: ciprofloxacin, meropenem, imipenem, amikacin, tobramycin, aztreonam, piperacillin/tazobactam, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, cefepime and colistin. The resistance mechanisms present in each strain were assessed by PCR, sequencing and quantitative RT-PCR. Molecular epidemiology was determined by MLST. Phylogenetic analysis was carried out using the eBURST algorithm. RESULTS: High levels of resistance to ciprofloxacin (44.19%) were found. Mutations in the gyrA, gyrB, parC and parE genes were detected in ciprofloxacin-resistant P. aeruginosa strains. The number of mutated QRDR genes was related to increased MIC. Different ß-lactamases were detected: blaOXA50, blaGES-2, blaIMI-2 and blaGIM-1. The aac(3)-Ia, aac(3)-Ic, aac(6″)-Ib and ant(2″)-Ia genes were associated with aminoglycoside-resistant strains. The gene expression analysis showed overproduction of the MexAB-OprM efflux system (46.5%) over the other efflux system. The most frequently detected clones were ST619, ST676, ST532 and ST109. CONCLUSIONS: Resistance to first-line antimicrobials recommended in BE guidelines could threaten the treatment of BE and the eradication of P. aeruginosa, contributing to chronic infection.

Cardiovascular Events During and After Bronchiectasis Exacerbations and Long-term Mortality.

BACKGROUND: Population-based and retrospective studies have shown that risk for cardiovascular events such as arrythmias, ischemic episodes, or heart failure, increase during and after bronchiectasis exacerbations. RESEARCH QUESTION: What are the risk factors for cardiovascular events (CVE) during and after bronchiectasis exacerbations and their impact on mortality? STUDY DESIGN AND METHODS: This was a post hoc retrospective analysis of a prospective observational study of 250 patients with bronchiectasis at two tertiary care hospitals. Only the first exacerbation was considered for each patient, collecting demographic, comorbidity, and severity data. The main outcomes were the appearance of CVE and mortality. Risk factors for CVE were analyzed using a semi-competing risks model. RESULTS: During a median follow-up of 35 months, 74 (29.6%) patients had a CVE and 93 (37.2%) died. Semi-competing risk analysis indicated that age, arterial hypertension, COPD, and potentially severe exacerbations significantly increased the risk for developing CVE. Compared with patients without CVE, those with CVE had higher mortality. INTERPRETATION: Demographic factors and comorbidities are risk factors for the development of CVE after an acute exacerbation of bronchiectasis. The appearance of CVE worsens long-term prognosis.

[Respiratory physiotherapy in post-COVID-19: a decision-making algorithm for clinical practice]. / Fisioterapia respiratoria post-COVID-19: algoritmo de decisión terapéutica.

The outbreak of COVID-19 has posed a great challenge for the healthcare system which has been later aggravated by the need of managing clinical manifestations and potential sequelae in COVID-19 survivors. In this context, respiratory Physiotherapy emerges as a cornerstone in the interdisciplinary management warranted in this population. Given that the implementation and resources available for the interdisciplinary therapeutic interventions in Spain is scarce, it is essential to perform a comprehensive, exhaustive and personalised assessment. This will allow us to establish more accurate selection criteria in order to optimise the use of existing human and material resources. To this end, we propose here a decision-making algorithm for clinical practice to assess the clinical manifestations in people recovered from COVID-19 based on well-established, validated tests and assessment tools. This algorithm can be used at any clinical practice environment (primary care/community or hospital-based), combined with a patient-centered model and the use of community and e-Health resources and its application to improve the Physiotherapy care of these patients in the COVID-19 era.

Pseudomonas aeruginosa in Bronchiectasis.

Pseudomonas aeruginosa (PA) in patients with bronchiectasis (BE) is associated with a poor outcome and quality of life, and its presence is considered a marker of disease severity. This opportunistic pathogen is known for its ability to produce biofilms on biotic or abiotic surfaces and to survive environmental stress exerted by antimicrobials, inflammation, and nutrient or oxygen depletion. The presence of PA biofilms has been linked to chronic respiratory infection in cystic fibrosis but not in BE. There is considerable inconsistency in the reported infection/eradication rates of PA and chronic PA. In addition, inadequate antimicrobial treatment may potentiate the progression from intermittent to chronic infection and also the emergence of antibiotic resistance. A better comprehension of the pathophysiology of PA infections and its implications for BE is urgently needed. This can drive improvements in diagnostic accuracy, can move us toward a new consensus definition of chronic infection, can better define the follow-up of patients at risk of PA, and can achieve more successful eradication rates. In addition, the new technological advances regarding molecular diagnostics, -omics, and biomarkers require us to reconsider our traditional concepts.

Exacerbations and Changes in Physical Activity and Sedentary Behaviour in Patients with Bronchiectasis after 1 Year.

BACKGROUND: Low physical activity and high sedentary behaviour in patients with bronchiectasis are associated with hospitalisation over one year. However, the factors associated with longitudinal changes in physical activity and sedentary behaviour have not been explored. We aimed to identify clinical and sociodemographic characteristics related to a change in physical activity and sedentary behaviour in patients with bronchiectasis after one year. METHODS: This was a prospective observational study during which physical activity measurements were recorded using a SenseWear Armband for one week at baseline and at one year. At each assessment point, patients were classified as active or inactive (measured as steps per day) and as sedentary or not sedentary (measured as sedentary time). RESULTS: 53 patients with bronchiectasis were analysed, and after one year, 18 (34%) had worse activity and sedentary levels. Specifically, 10 patients became inactive and sedentary. Multivariable analysis showed that the number of exacerbations during the follow-up period was the only outcome independently associated with change to higher inactivity and sedentary behaviour (odds ratio (OR), 2.19; 95% CI, 1.12 to 4.28). CONCLUSIONS: The number of exacerbations in patients with bronchiectasis was associated with changes in physical activity and sedentary behaviour. Exacerbation prevention may appear as a key factor in relation to physical activity and sedentary behaviour in patients with bronchiectasis.

Aetiological diagnosis in new adult outpatients with bronchiectasis:role of predictors derived from real life experience.

BACKGROUND: In adult patients with bronchiectasis (BE) the identification of the underlying aetiology may be difficult. In a new patient with BE the performance of a panel of tests is recommended, even though this practice may be expensive and the level of evidence supporting is low. We aimed to identify a panel of variables able to predict the aetiological diagnosis of BE. METHODS: Our prospective study derived from our real-life experience on the management of adult stable BE outpatients. We recorded variables concerning clinical, radiological, microbiological and laboratory features. We identified five groups of aetiological diagnosis of BE (idiopathic, post-infective, COPD, asthma and non-common diseases [immunodeficiency or other rare conditions]). Multivariate models were used to identify predictors of each aetiological diagnosis. The suitability of performing a specific test for the diagnosis was also considered. RESULTS: We enrolled 354 patients with a new diagnosis of BE. Patients with different aetiological causes differed significantly with regard to age, sex, smoking habit, comorbidities, dyspnoea perception, airflow obstruction and severity scores. Various predictors were assessed, including sex, previous respiratory infections, diffuse localization of BE, risk scores, and laboratory variables (sodium and eosinophils). The levels of autoantibodies or immunoglobulins were reserved for the diagnosis of non-common disease. CONCLUSION: Our research confirms that some predictors are specific for the aetiological diagnosis of BE. The possibility of integrating this information may represent a useful tool for the diagnosis. The execution of certain specific tests should be reserved for patients with a non-common disease.

Association between physical activity and risk of hospitalisation in bronchiectasis.

BACKGROUND: Patients with bronchiectasis have a less active lifestyle than healthy peers, but the association with hospital admission has not been explored. The aim of this study was to investigate the association between 1) any physical activity variable; and 2) sedentary time, with hospitalisation due to exacerbation in adults with bronchiectasis. METHODS: In this prospective observational study, baseline lung function, quality of life, exercise tolerance, severity of bronchiectasis and physical activity were recorded. Physical activity was objectively assessed over a week using a SenseWear armband and the results were expressed in steps·day-1 and sedentary time. Number of hospitalisations due to a bronchiectasis exacerbation and time to first event were recorded after 1-year follow-up. RESULTS: Sixty-four patients with bronchiectasis were analysed, of whom 15 (23%) were hospitalised during the follow-up. Hospitalised patients showed poor baseline clinical and severity outcomes, fewer steps walked per day and more sedentary behaviour than the non-hospitalised group. Patients who walked ≤6290 steps·day-1 or spent ≥7.8 h·day-1 in sedentary behaviour had an increased risk of hospital admission due to bronchiectasis exacerbation at 1-year follow-up. Specifically, ≥7.8 h·day-1 of sedentary behaviour was associated with a 5.9-fold higher risk of hospital admission in the following year. CONCLUSIONS: Low levels of physical activity and high sedentary time at baseline were associated with a higher risk of hospitalisation due to bronchiectasis exacerbation. If these findings are validated in future studies, it might be appropriate to include physical activity and sedentary behaviour as an item in severity scores.

Reliability and Minimum Important Difference of Sputum Weight in Bronchiectasis.

BACKGROUND: Despite the widespread use of sputum weight to assess the effect of airway clearance interventions, its psychometric properties have not been evaluated. The purpose of this ad hoc analysis was to determine the test-retest reliability of 24-h sputum weight in clinically stable individuals with bronchiectasis. This study also aimed to estimate the minimum important difference of 24-h sputum weight after an airway clearance session in subjects with bronchiectasis. METHODS: Sixty subjects were included in the 24-h test-retest cohort, 42 of whom were part of the airway clearance cohort. For the 24-h test-retest cohort, spontaneously expectorated sputum was collected over 24 h on 2 different days without any airway clearance interventions. For the airway clearance cohort, sputum expectoration was also collected during 3 airway clearance sessions and over the 24 h following these interventions. Intraclass correlation coefficient (ICC3,1) and Bland-Altman analysis were used to assess reliability. The minimum important difference was calculated using distribution-based and anchor-based methods, with cough impact as assessed with the Leicester Cough Questionnaire and the global rating of change as anchors. RESULTS: The reliability was acceptable (ICC3,1 = 0.75) for sputum weight over 24 h without any intervention. The agreement level was wide, particularly for high levels of sputum expectoration. The minimum important difference of the sputum collected in the 24 h after the intervention from baseline was -6.4 g (about -17%), determined using distribution-based methods. There was no correlation between sputum weight and the anchors, thus the anchor-based methodology could not be used. CONCLUSIONS: Multiple measurements should be considered to increase the agreement when sputum weight is used as an outcome measure for short periods in people with bronchiectasis. A reduction of 6.4 g (or 17% from baseline) in sputum collected during the 24 h after the airway clearance intervention may be considered the minimum important difference in people with bronchiectasis. (ClinicalTrials.gov registration NCT02392663; NCT01854788; NCT02614300.).

Clinical Factors Associated with a Shorter or Longer Course of Antibiotic Treatment in Patients with Exacerbations of Bronchiectasis: A Prospective Cohort Study.

BACKGROUND: Bronchiectasis exacerbations are often treated with prolonged antibiotic use, even though there is limited evidence for this approach. We therefore aimed to investigate the baseline clinical and microbiological findings associated with long courses of antibiotic treatment in exacerbated bronchiectasis patients. METHODS: This was a bi-centric prospective observational study of bronchiectasis exacerbated adults. We compared groups receiving short (≤14 days) and long (15-21 days) courses of antibiotic treatment. RESULTS: We enrolled 191 patients (mean age 72 (63, 79) years; 108 (56.5%) females), of whom 132 (69%) and 59 (31%) received short and long courses of antibiotics, respectively. Multivariable logistic regression of the baseline variables showed that long-term oxygen therapy (LTOT), moderate-severe exacerbations, and microbiological isolation of Pseudomonas aeruginosa were associated with long courses of antibiotic therapy. When we excluded patients with a diagnosis of community-acquired pneumonia (n = 49), in the model we found that an etiology of P. aeruginosa remained as factor associated with longer antibiotic treatment, with a moderate and a severe FACED score and the presence of arrhythmia as comorbidity at baseline. CONCLUSIONS: Decisions about the duration of antibiotic therapy should be guided by clinical and microbiological assessments of patients with infective exacerbations.

Mucoid Pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION AND AIM: Pseudomonas aeruginosa could acquire a mucoid phenotype due to mutations in mucA (mucoid Pseudomonas aeruginosa - mPA) that is a hallmark of poor prognosis in patients with bronchiectasis. Despite the higher prevalence of Pseudomonas aeruginosa in bronchiectasis, how mPA and non-mucoid Pseudomonas aeruginosa (non-mPA) phenotypes could affect viscoelastic properties of sputum is unknown. Our aim was to determine the relationship between Pseudomonas aeruginosa phenotypes isolation, the viscoelastic properties of sputum and the clinical outcomes in patients with bronchiectasis. METHODS: A cross-sectional study was conducted of sputum samples obtained by spontaneous expectoration and sent for microbiology and rheology analysis. Elasticity and viscosity were measured at two oscillatory frequencies (1 and 100 rad/s). Socio-demographic and clinical data were recorded. RESULTS: We analyzed 17 patients with mPA, 14 with non-mPA and 17 with no organism reported (NOR). Compared with the NOR group, the mPA group showed higher elasticity (median 10.30 vs. 5.70, p = 0.023), viscosity (2.40 vs. 1.50, p = 0.039), and stiffness (10.70 vs. 6.00, p = 0.024). Values in the mPA group tended to be higher compared with non-mPA. Clinically, the mPA group showed greater hospitalizations during the previous year and greater affected lobes than the non-mPA and NOR groups. CONCLUSIONS: The mPA phenotype is associated with increased elasticity, viscosity and stiffness of bronchiectatic sputum. Viscoelastic properties could be used as a marker of poor mucociliary clearance in mPA, with potentially important clinical implications.

Pneumonic and non-pneumonic exacerbations in bronchiectasis: Clinical and microbiological differences.

OBJECTIVES: Despite the clinical relevance of exacerbations in bronchiectasis (BE), little is known about the microbiology and outcomes of pneumonic (CAP) vs. non-pneumonic (NOCAP) exacerbations. METHODS: This study compares clinical and microbiological characteristics of CAP vs. NOCAP in adults with BE. We performed a multicenter prospective observational study of consecutive cases of NOCAP and CAP from four Spanish hospitals (2011-2015). RESULTS: We recruited 144 patients, 47 of them CAP (33%) cases. CAP patients were older, with a larger representation of males, more comorbidities, higher arterial hypertension and COPD but less chronic bronchial infection and previous history of exacerbations. Clinical presentation was similar, excepting creatinine, C-reactive protein (C-RP), glucose and leukocytes which were higher in CAP. C-RP of 8.38 mg/dL showed a significant predictive discrimination for CAP. Streptococcus pneumoniae and Pseudomonas aeruginosa were the first causes of CAP and NOCAP, respectively. The rate of microbiological concordance with previous chronic bronchial infection was variable. Main clinical outcomes (mortality, length of stay, etc.) were similar in the two groups. Chronic bronchial infection and history of frequent exacerbations (≥ 2/year) were associated with a reduced risk of CAP. CONCLUSIONS: CAP and NOCAP in BE had similar clinical presentation with the exception of fever, leukocytosis, and C-RP. Microbiology also differed. A cut-off value of C-RP ≥ 8.38 mg/dL can predict CAP in bronchiectasis.