Abstract: Bronchiectasis is a disease associated with chronic progressive and irreversible dilatation of the bronchi and is characterised by chronic infection and associated inflammation. The prevalence of bronchiectasis is age-related and there is some geographical variation in incidence, prevalence and clinical features. Most bronchiectasis is reported to be idiopathic however post-infectious aetiologies dominate across Asia especially secondary to tuberculosis. Most focus to date has been on the study of airway bacteria, both as colonisers and causes of exacerbations. Modern molecular technologies including next generation sequencing (NGS) have become invaluable tools to identify microorganisms directly from sputum and which are difficult to culture using traditional agar based methods. These have provided important insight into our understanding of emerging pathogens in the airways of people with bronchiectasis and the geographical differences that occur. The contribution of the lung microbiome, its ethnic variation, and subsequent roles in disease progression and response to therapy across geographic regions warrant further investigation. This review summarises the known geographical differences in the aetiology, epidemiology and microbiology of bronchiectasis. Further, we highlight the opportunities offered by emerging molecular technologies such as -omics to further dissect out important ethnic differences in the prognosis and management of bronchiectasis.

Abstract: Pseudomonas aeruginosa is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease. This study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of P. aeruginosa chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed. The prevalence of P. aeruginosa chronic infection was 15.0% (n=389). P. aeruginosa was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53–2.66; p

Abstract: Bronchiectasis is a clinical and radiological diagnosis associated with cough, sputum production and recurrent respiratory infections. The clinical presentation inevitably overlaps with other respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). In addition, 4–72% of patients with severe COPD are found to have radiological bronchiectasis on computed tomography, with similar frequencies (20–30%) now being reported in cohorts with severe or uncontrolled asthma. Co-diagnosis of bronchiectasis with another airway disease is associated with increased lung inflammation, frequent exacerbations, worse lung function and higher mortality. In addition, many patients with all three disorders have chronic rhinosinusitis and upper airway disease, resulting in a complex “mixed airway” phenotype. The management of asthma, bronchiectasis, COPD and upper airway diseases has traditionally been outlined in separate guidelines for each individual disorder. Recognition that the majority of patients have one or more overlapping pathologies requires that we re-evaluate how we treat airway disease. The concept of treatable traits promotes a holistic, pathophysiology-based approach to treatment rather than a syndromic approach and may be more appropriate for patients with overlapping features. Here, we review the current clinical definition, diagnosis, management and future directions for the overlap between bronchiectasis and other airway diseases.

Abstract: Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described.Object...

Abstract: Pseudomonas aeruginosa is a challenging bacterium to treat due to its intrinsic resistance to the antibiotics used most frequently in patients with community-acquired pneumonia (CAP). Data about the global burden and risk factors associated with P. aeruginosa-CAP are limited. We assessed the multinational burden and specific risk factors associated with P. aeruginosa-CAP. We enrolled 3193 patients in 54 countries with confirmed diagnosis of CAP who underwent microbiological testing at admission. Prevalence was calculated according to the identification of P. aeruginosa. Logistic regression analysis was used to identify risk factors for antibiotic-susceptible and antibiotic-resistant P. aeruginosa-CAP. The prevalence of P. aeruginosa and antibiotic-resistant P. aeruginosa-CAP was 4.2% and 2.0%, respectively. The rate of P. aeruginosa CAP in patients with prior infection/colonisation due to P. aeruginosa and at least one of the three independently associated chronic lung diseases (i.e. tracheostomy, bronchiectasis and/or very severe chronic obstructive pulmonary disease) was 67%. In contrast, the rate of P. aeruginosa-CAP was 2% in patients without prior P. aeruginosa infection/colonisation and none of the selected chronic lung diseases. The multinational prevalence of P. aeruginosa-CAP is low. The risk factors identified in this study may guide healthcare professionals in deciding empirical antibiotic coverage for CAP patients.

Abstract: Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients. This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis. A total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49–5.84; p = 0.002), greater severity of asthma (OR, 2.43; 95% CI, 1.29–4.57; p = 0.006), at least one previous episode of pneumonia (OR, 2.42; 95% CI, 1.03–5.69; p = 0.044), and lower levels of FeNO (OR, 0.98; 95% CI, 0.97–0.99; p = 0.016). The NOPES score was developed on the basis of these variables (FeNO[cut off point 20.5 ppb], Pneumonia, Expectoration and asthma Severity), and it ranges from 0 to 4 points, where 0 means “no risk” and 4 corresponds to “high risk”. The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%. Almost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma.

Abstract: Airway mucus hypersecretion is one of the most important characteristics of chronic airway inflammatory diseases. Evaluating and managing airway mucus hypersecretion is of great importance for patients with chronic airway inflammatory diseases. This consensus statement describes the pathogenesis, clinical features, and the management of airway mucus hypersecretion in patients with chronic airway inflammatory diseases in the People's Republic of China. The statement has been written particularly for respiratory researchers, pulmonary physicians, and patients.

Abstract: Immunoglobulin replacement therapy (IGRT) has contributed critically to the management of primary antibody deficiencies (PAD) and the decrease in pneumonia rate. However, despite adequate IGRT and improved prognosis, patients with PAD continue to experience recurrent respiratory tract infections, leading to bronchiectasis and continuing decline in lung function with a severe impact on their quality of life. Moreover, non-infectious inflammatory and interstitial lung complications, such as granulomatous-lymphocytic interstitial lung disease, contribute substantially to the overall morbidity of PAD. These conditions develop much more often than appreciated and represent a major therapeutic challenge. Therefore, a regular assessment of the structural and functional condition of the lung and the upper airways with appropriate treatment is required to minimize the deterioration of lung function. This work summarizes the knowledge on lung complications in PAD and discusses the currently available diagnostic tools and treatment options.

Abstract: Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.

Abstract: Gender differences in chronic respiratory disease, including cystic fibrosis and non-cystic fibrosis bronchiectasis are clinically apparent and of increasing importance. Differences in disease prevalence, severity and outcome are all described, however, the precise cause of the gender dichotomy and their associated underlying mechanisms have been poorly characterised. A lack of dedicated clinical and epidemiological research focused in this area has led to a paucity of data and therefore a lack of understanding of its key drivers. Diagnosis, disease pathogenesis and treatment response are all complex but important aspects of bronchiectasis with an evident gender bias. Broadening our understanding of the interplay between microbiology, host physiology and the environment in the context of chronic lung diseases, such as bronchiectasis, is critical to unravelling mechanisms driving the observed gender differences. In this review, epidemiological, biological and environmental evidence related to gender in bronchiectasis is summarised. This illustrates gender differences as a “real issue” with the objective of mapping out a future framework upon which a gender-tailored medical approach may be incorporated into the diagnosis, monitoring and treatment of bronchiectasis. Key points CF and non-CF bronchiectasis are complex, multifactorial chronic pulmonary diseases with gender-specific differences in their prevalence, clinical presentation and disease severity. Microbiology and host physiology (immune and inflammatory responses) are essential aspects of bronchiectasis that are influenced by gender. Sex steroid hormones vary in type, fluctuating pattern and concentration throughout life and between the genders with a potential central role in bronchiectasis-related gender differences. Gender-focused clinical and/or therapeutic intervention has the potential to narrow the observed gender gap occurring in bronchiectasis-related lung disease. Educational aims To summarise the existing knowledge base of gender-related differences in CF and non-CF bronchiectasis. To highlight key areas of importance in the diagnosis, monitoring and treatment of bronchiectasis that is amenable to clinical and/or pharmacological intervention to narrow the existing “gender gap”.

Abstract: Rationale: Nontuberculous mycobacterial (NTM) pulmonary disease prevalence is increasingObjectives: To determine the association between the use of inhaled corticosteroids and the likelihood of NT

Abstract: Background Bronchiectasis is increasingly being identified in patients with severe asthma and could contribute to disease severity. Objective To determine the prevalence of bronchiectasis in a population of patients with severe asthma and to better characterize the clinical features of these patients and their outcomes. Methods We retrospectively reviewed the medical files of 184 subjects with confirmed severe asthma who had undergone high-resolution thoracic computed tomography and compared the characteristics and outcomes of subjects with and without bronchiectasis. Results Bronchiectasis was identified in 86 patients (47%). These patients had concomitant hypersensitivity to nonsteroidal anti-inflammatory drugs (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.00–5.03) and gastroesophageal reflux disease (OR 1.89, 95% CI 1.05–3.41) more frequently than subjects without bronchiectasis, but had less atopic dermatitis (OR 0.188, 95% CI 0.04–0.88). Subjects with bronchiectasis were more frequently hospitalized for asthma exacerbations (OR 2.09, 95% CI 1.08–4.05) and had higher blood eosinophil levels (464 vs 338; P = .005) than subjects without bronchiectasis. Conclusion Our study suggests that in subjects with severe asthma, the presence of bronchiectasis is associated with more frequent hospitalizations, concomitant gastroesophageal reflux disease, hypersensitivity to nonsteroidal anti-inflammatory drugs, and higher blood eosinophil counts. Bronchiectasis could represent an additional phenotypic feature of severe eosinophilic asthma.

Abstract: IL-8-dependent inflammation is a hallmark of host lung innate immunity to bacterial pathogens, yet in many human lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and pulmonary fibrosis, there are progressive, irreversible, pathological changes associated with elevated levels of IL-8 in the lung. To better understand the duality of IL-8-dependent host immunity to bacterial infection and lung pathology, we expressed human IL-8 transgenically in murine bronchial epithelium, and investigated the impact of overexpression on lung bacterial clearance, host immunity, and lung pathology and function. Persistent IL-8 expression in bronchial epithelium resulted in neutrophilia, neutrophil maturation and activation, and chemotaxis. There was enhanced protection against challenge with Pseudomonas aeruginosa, and significant changes in baseline expression of innate and adaptive immunity transcripts for Ccl5, Tlr6, IL-2, and Tlr1. There was increased expression of Tbet and Foxp3 in response to the Pseudomonas antigen OprF, indicating a regulatory T-cell phenotype. However, this enhanced bacterial immunity came at a high price of progressive lung remodeling, with increased inflammation, mucus hypersecretion, and fibrosis. There was increased expression of Ccl3 and reduced expression of Claudin 18 and F11r, with damage to epithelial organization leading to leaky tight junctions, all of which resulted in impaired lung function with reduced compliance, increased resistance, and bronchial hyperreactivity as measured by whole-body plethysmography. These results show that IL-8 overexpression in the bronchial epithelium benefits lung immunity to bacterial infection, but specifically drives lung damage through persistent inflammation, lung remodeling, and damaged tight junctions, leading to impaired lung function.

Abstract: Introduction The presence of bronchiectasis in patients with asthma varies in different reports, while a clear aetiological relation has not been precisely established Objectives To investigate the presence of bronchiectasis in patients with severe uncontrolled asthma and examine whether they contribute to the severity of asthma Methods Patients with severe asthma were prospectively recruited HRCT of the chest was performed to identify and grade bronchiectasis using the ‘Smith’ radiology scale Investigation of the underlying cause was carried out for patients with bronchiectasis in order to exclude aetiologies other than asthma The Statistical Package for the Social Sciences (SPSS), version 21, was used Results Forty patients were studied, 28 women, mean age (±SD) 579 years (±124) Mean ACT score was 142(±49) Main symptoms were: wheezing (95%), cough (92%), dysponea (92%) and sputum production (72%) Mean duration of asthma was 165(±115) years, exacerbations: 44(±27)/year In 27 patients (675%) bronchiectasis was diagnosed In nine patients (225%) pathogens were cultured in sputum (mainly Pseudomonas aeruginosa, Haemophilus influenzae) Patients with sputum production and pathogens in sputum cultures had a higher Smith score compared to those without expectoration and without pathogens, respectively (P = 005, P < 0001) No correlation was found between the extent of bronchiectasis and lung function The radiological severity of bronchiectasis was correlated with the antibiotic courses/year (P = 002) Conclusion Bronchiectasis is common in patients with severe asthma Sputum production and pathogen isolation in sputum may indicate the presence of bronchiectasis which seems to contribute to the severity of asthma

Abstract: The Activated Phosphoinositide 3-kinase δ Syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (encoding p110δ: APDS1 or PASLI-CD) and PIK3R1 (encoding p85α: APDS2 or PASLI-R1). Whilst the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe. Infections of the ears, sinuses and upper and lower respiratory tracts are the earliest and most frequent manifestation of APDS, secondary to both respiratory viruses and to bacterial pathogens typical of defective B cell function. End organ damage in the form of small airways disease and bronchiectasis frequently complicates APDS, but despite documented T cell defects, opportunistic infections have rarely been observed. Antimicrobial (principally antibiotic) prophylaxis and/or immunoglobulin replacement have been widely used to reduce the frequency and severity of respiratory infection in APDS, but outcome data to confirm the efficacy of these interventions is limited. Despite these measures, APDS patients are often afflicted by benign lymphoproliferative disease, which may present in the respiratory system as tonsillar/adenoidal enlargement, mediastinal lymphadenopathy or mucosal nodular lymphoid hyperplasia, potentially causing airways obstruction and compounding the infection phenotype. Treatment with rapamycin and PI3Kδ inhibitors has been reported to be of benefit in benign lymphoproliferation, but hematopoietic stem cell transplantation (ideally undertaken before permanent airway damage is established) remains the only curative treatment for APDS.

Abstract: Background Bronchiectasis is a chronic airway disease characterised by a destructive cycle of recurrent airway infection, inflammation and tissue damage. Antibiotics are a main treatment for bronchiectasis. The aim of continuous therapy with prophylactic antibiotics is to suppress bacterial load, but bacteria may become resistant to the antibiotic, leading to a loss of effectiveness. On the other hand, intermittent prophylactic antibiotics, given over a predefined duration and interval, may reduce antibiotic selection pressure and reduce or prevent the development of resistance. This systematic review aimed to evaluate the current evidence for studies comparing continuous versus intermittent administration of antibiotic treatment in bronchiectasis in terms of clinical efficacy, the emergence of resistance and serious adverse events. Objectives To evaluate the effectiveness of continuous versus intermittent antibiotics in the treatment of adults and children with bronchiectasis, using the primary outcomes of exacerbations, antibiotic resistance and serious adverse events. Search methods On 1 August 2017 and 4 May 2018 we searched the Cochrane Airways Review Group Specialised Register (CAGR), CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. On 25 September 2017 and 4 May 2018 we also searched www.clinicaltrials.gov, the World Health Organization (WHO) trials portal, conference proceedings and the reference lists of existing systematic reviews. Selection criteria We planned to include randomised controlled trials (RCTs) of adults or children with bronchiectasis that compared continuous versus intermittent administration of long-term prophylactic antibiotics of at least three months' duration. We considered eligible studies reported as full-text articles, as abstracts only and unpublished data. Data collection and analysis Two review authors independently screened the search results and full-text reports. Main results We identified 268 unique records. Of these we retrieved and examined 126 full-text reports, representing 114 studies, but none of these studies met our inclusion criteria. Authors' conclusions No randomised controlled trials have compared the effectiveness and risks of continuous antibiotic therapy versus intermittent antibiotic therapy for bronchiectasis. High-quality clinical trials are needed to establish which of these interventions is more effective for reducing the frequency and duration of exacerbations, antibiotic resistance and the occurrence of serious adverse events. Plain language summary Are antibiotics more effective when given continuously or intermittently to people with bronchiectasis? Background Bronchiectasis is an incurable lung disease characterised by repeated chest infections. Antibiotics are a main form of treatment and can be taken long term to prevent chest infections from developing. This could be continuously or intermittently for a fixed period of time. However, we do not currently know which approach is the most effective for reducing the frequency and duration of exacerbations, managing antibiotic resistance and minimising side effects. Study Characteristics On 1 August 2017 we searched a wide range of sources to find clinical trials for our review. We found 268 potentially relevant results but on closer examination none of the studies met our review criteria and none could be included. Authors' conclusions There is no high-quality evidence about whether continuously administered or intermittently administered antibiotics are safer and more helpful for people with bronchiectasis. More research is needed to evaluate which one of these methods is better for reducing chest infections, limiting resistance to antibiotic therapy and reducing serious side effects.

Abstract: Background The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of death according to the HTLV-1c proviral load (pVL). Methodology/Principal findings 840 Indigenous adults (discharge diagnosis of bronchiectasis, 154) were recruited to a hospital-based prospective cohort. Baseline HTLV-1c pVL were determined and the results of chest computed tomography and clinical details reviewed. The odds of an association between HTLV-1 infection and bronchiectasis or bronchitis/bronchiolitis were calculated, and the impact of HTLV-1c pVL on the risk of death was measured. Radiologically defined bronchiectasis and bronchitis/bronchiolitis were significantly more common among HTLV-1-infected subjects (adjusted odds ratio = 2.9; 95% CI, 2.0, 4.3). Median HTLV-1c pVL for subjects with airways inflammation was 16-fold higher than that of asymptomatic subjects. There were 151 deaths during 2,140 person-years of follow-up (maximum follow-up 8.13 years). Mortality rates were higher among subjects with HTLV-1c pVL ≥1000 copies per 105 peripheral blood leukocytes (log-rank χ2 (2df) = 6.63, p = 0.036) compared to those with lower HTLV-1c pVL or uninfected subjects. Excess mortality was largely due to bronchiectasis-related deaths (adjusted HR 4.31; 95% CI, 1.78, 10.42 versus uninfected). Conclusion/Significance Higher HTLV-1c pVL was strongly associated with radiologically defined airways inflammation and with death due to complications of bronchiectasis. An increased risk of death due to an HTLV-1 associated inflammatory disease has not been demonstrated previously. Our findings indicate that mortality associated with HTLV-1c infection may be higher than has been previously appreciated. Further prospective studies are needed to determine whether these results can be generalized to other HTLV-1 endemic areas.

Abstract: Background Chronic respiratory symptoms are common among children living with human immunodeficiency virus (HIV). We investigated the radiological features of chronic lung disease in children aged 6–16 years receiving antiretroviral therapy for ≥6 months in Harare, Zimbabwe. Methods Consecutive participants from a HIV clinic underwent clinical assessment and chest radiography. Participants with an abnormal chest radiograph (assessed by a clinician) and/or those meeting a clinical case definition for chronic lung disease underwent high-resolution computed tomography (HRCT). Radiological studies were scored independently and blindly by 2 thoracic radiologists. Relationships between radiological abnormalities and lung function were examined. Results Among 193 participants (46% female; median age, 11.2 years; interquartile range, 9.0–12.8 years), the median CD4 cell count was 720/µL (473–947/µL), and 79% had a human immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest radiographic finding was ring/tramline opacities (55 of 193 participants; 29%). HRCT scans were evaluated in 84 participants (69%); decreased attenuation (present in 43%) was the dominant abnormality seen. The extent of decreased attenuation was strongly correlated with both the severity and extent of bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased attenuation was also negatively correlated with forced expiratory volume in first second of expiration (rs = –0.52), forced vital capacity (rs = –0.42), and forced expiratory flow, midexpiratory phase (rs = –0.42) (P < .001 for all). Conclusions The HRCT findings strongly suggest that obliterative bronchiolitis may be the major cause of chronic lung disease in our cohort. Further studies to understand the pathogenesis and natural history are urgently needed.

Abstract: Inflammatory bowel disease (IBD) is a form of chronic inflammation of the gastrointestinal tract, including two major entities: ulcerative colitis and Crohn's disease. Although intestinal imaging of IBD is well known, imaging of extraintestinal manifestations is not extensively covered. In particular, the spectrum of IBD-associated or related changes in the chest is broad and may mimic other conditions. The common embryonic origin of intestine and lungs from the foregut, autoimmunity, smoking, and bacterial translocation from the colon may all be involved in the pathogenesis of these manifestations in IBD patients. Chest involvement in IBD can present concomitant with or years after the onset of the bowel disease even postcolectomy and can affect more than one thoracic structure. The purpose of the present paper is to present the different radiological spectrum of IBD-related chest manifestations, including lung parenchyma, airways, serosal surfaces, and pulmonary vasculature. The most prevalent and distinctive pattern of respiratory involvement is large airway inflammation, followed by lung alterations. Pulmonary manifestations are mainly detected by pulmonary function tests and high-resolution computed tomography (HRCT). It is desirable that radiologists know the various radiological patterns of possible respiratory involvement in such patients, especially at HRCT. It is essential for radiologists to work in multidisciplinary teams in order to establish the correct diagnosis and treatment, which rests on corticosteroids at variance with any other form of bronchiectasis.

Abstract: Cystic fibrosis (CF) lung disease progressively worsens from infancy to adulthood. Disease-driven changes in early CF airway fluid metabolites may identify therapeutic targets to curb progression. CF patients aged 12–38 months (n=24; three out of 24 later denoted as CF screen positive, inconclusive diagnosis) received chest computed tomography scans, scored by the Perth–Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) method to quantify total lung disease (PRAGMA-%Dis) and components such as bronchiectasis (PRAGMA-%Bx). Small molecules in bronchoalveolar lavage fluid (BALF) were measured with high-resolution accurate-mass metabolomics. Myeloperoxidase (MPO) was quantified by ELISA and activity assays. Increased PRAGMA-%Dis was driven by bronchiectasis and correlated with airway neutrophils. PRAGMA-%Dis correlated with 104 metabolomic features (p BALF MetO associates with structural lung damage, airway neutrophils and MPO in early CF. Further studies are needed to establish whether methionine oxidation directly contributes to early CF lung disease and explore potential therapeutic targets indicated by these findings.

Abstract: Bronchiectasis is a chronic respiratory disease characterised by a syndrome of productive cough and recurrent respiratory infections due to permanent dilatation of the bronchi. Bronchiectasis represents the final common pathway of different disorders, some of which may require specific treatment. Therefore, promptly identifying the aetiology of bronchiectasis is recommended by the European Respiratory Society guidelines. The clinical history and high-resolution computed tomography (HRCT) features can be useful to detect the underlying causes. Despite a strong focus on this aspect of treatment a high proportion of patients remain classified as “idiopathic”. Important underlying conditions that are treatable are frequently not identified for prolonged periods of time. The European Respiratory Society guidelines for bronchiectasis recommend a minimal bundle of tests for diagnosing the cause of bronchiectasis, consisting of immunoglobulins, testing for allergic bronchopulmonary aspergillosis and full blood count. Other testing is recommended to be conducted based on the clinical history, radiological features and severity of disease. Therefore it is essential to teach clinicians how to recognise the “clinical phenotypes” of bronchiectasis that require specific testing. This article will present the initial investigation and management of bronchiectasis focussing particularly on the HRCT features and clinical features that allow recognition of specific causes.

Abstract: Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently.

Abstract: Objectives This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. Methods Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed. Results Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types. Conclusions Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

Abstract: Background Bronchiectasis is characterized by a progressive structural lung damage, recurrent infections and chronic inflammation which compromise the exertion tolerance, and may have an impact on skeletal muscle function and physical function. Objective The purpose of this study was to compare peripheral muscle strength, exercise capacity, and physical activity in daily life between participants with bronchiectasis and controls and to investigate the determinants of the peripheral muscle strength and physical activity in daily life in bronchiectasis. Design This study used a cross-sectional design. Methods The participants' quadriceps femoris and biceps brachii muscle strength was measured. They performed the incremental shuttle walk test (ISWT) and cardiopulmonary exercise testing, and the number of steps/day was measured by a pedometer. Results Participants had reduced quadriceps femoris muscle strength (mean difference to control group = 7 kg, 95% CI = 3.8-10.1 kg), biceps brachii muscle strength (2.1 kg, 95% CI = 0.7-3.4 kg), ISWT (227 m, 95% CI = 174-281 m), peak VO2 (6.4 ml/Kg/min, 95% CI = 4.0-8.7 ml/Kg/min), and number of steps/day (3,332 steps/day, 95% CI = 1,758-4,890 steps/day). A lower quadriceps femoris strength is independently associated to an older age, female sex, lower body mass index (BMI), higher score on the modified Medical Research Council scale, and shorter distance on the ISWT (R2 = 0.449). Biceps brachii strength is independently associated with sex, BMI, and dyspnea (R2 = 0.447). The determinants of number of daily steps were dyspnea and distance walked in ISWT, explaining only 27.7% of its variance. Limitations Number of steps per day was evaluated by a pedometer. Conclusions People with bronchiectasis have reduced peripheral muscle strength, and reduced aerobic and functional capacities, and they also are less active in daily life. Modifiable variables such as BMI, dyspnea, and distance walked on the ISWT are associated with peripheral muscle strength and physical activity in daily life.

Abstract: Bronchiectasis is a prevalent respiratory condition characterised by permanent and abnormal dilation of the lung airways (bronchi). There are a large variety of causative factors that have been identified for bronchiectasis; all of these compromise the function of the immune response to fight infection. A triggering factor may lead to the establishment of chronic infection in the lower respiratory tract. The bacteria responsible for the lower respiratory tract infection are usually found as commensals in the upper respiratory tract microbiome. The consequent inflammatory response to infection is largely responsible for the pathology of this condition. Both innate and adaptive immune responses are activated. The literature has highlighted the central role of neutrophils in the pathogenesis of bronchiectasis. Proteases produced in the lung by the inflammatory response damage the airways and lead to the pathological dilation that is the pathognomonic feature of bronchiectasis. The small airways demonstrate infiltration with lymphoid follicles that may contribute to localised small airway obstruction. Despite aggressive treatment, most patients will have persistent disease. Manipulating the immune response in bronchiectasis may potentially have therapeutic potential.

Abstract: Kartagener’s syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal ciliary structure or function leading to impaired ciliary motility is the main pathophysiologic problem in Kartagener’s syndrome. A 24-year-old man from Gondar town, North-West Ethiopia, presented to University of Gondar Hospital with recurrent episodes of nasal congestion with itching and paranasal discomfort, and productive cough for more than a decade. Clinical and imaging findings revealed chronic sinusitis, bronchiectasis, dextrocardia, and situs inversus. He was treated with orally administered antibiotics, mucolytic, and chest physiotherapy. He was symptomatically better with the above therapy, and started on a long-term low-dose prophylactic antibiotic. Patients with Kartagener’s syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener’s syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener’s syndrome is diagnosed.