Abstract: Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post–lung transplant setting over the past decade. Antibiotics currently marketed ...

Abstract: Rationale: Treatment of pulmonary nontuberculous mycobacteria, especially Mycobacterium abscessus, requires prolonged, multidrug regimens with high toxicity and suboptimal efficacy. Options for refractory disease are limited. Objectives: We reviewed the efficacy and toxicity of inhaled amikacin in patients with treatment-refractory nontuberculous mycobacterial lung disease. Methods: Records were queried to identify patients who had inhaled amikacin added to failing regimens. Lower airway microbiology, symptoms, and computed tomography scan changes were assessed together with reported toxicity. Measurements and Main Results: The majority (80%) of the 20 patients who met entry criteria were women; all had bronchiectasis, two had cystic fibrosis and one had primary ciliary dyskinesia. At initiation of inhaled amikacin, 15 were culture positive for M. abscessus and 5 for Mycobacterium avium complex and had received a median (range) of 60 (6, 190) months of mycobacterial treatment. Patients were followed for a median of 19 (1, 50) months. Eight (40%) patients had at least one negative culture and 5 (25%) had persistently negative cultures. A decrease in smear quantity was noted in 9 of 20 (45%) and in mycobacterial culture growth for 10 of 19 (53%). Symptom scores improved in nine (45%), were unchanged in seven (35%), and worsened in four (20%). Improvement on computed tomography scans was noted in 6 (30%), unchanged in 3 (15%), and worsened in 11 (55%). Seven (35%) stopped amikacin due to: ototoxicity in two (10%), hemoptysis in two (10%), and nephrotoxicity, persistent dysphonia, and vertigo in one each. Conclusions: In some patients with treatment-refractory pulmonary nontuberculous mycobacterial disease, the addition of inhaled amikacin was associated with microbiologic and/or symptomatic improvement; however, toxicity was common. Prospective evaluation of inhaled amikacin for mycobacterial disease is warranted.

Abstract: Rationale Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. Objectives To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George9s Respiratory Questionnaire, SGRQ). Methods Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18–85 years of age, baseline FEV 1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. Main results 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (−2.4 units, p=0.046). Adverse events were similar between groups. Conclusions Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. Trial registration number NCT00669331.

Abstract: While cystic fibrosis (CF) is the most common cause of bronchiectasis in childhood, non-CF bronchiectasis is associated with a wide variety of disorders. The objective of this study was to determine the relative prevalence and specific etiologies on non-CF bronchiectasis in childhood. EMBASE, Medline, OVID Cochrane Reviews, Directory of Open Access Journals, Open Science Directory, EPSCO information services, and OAlster were searched electronically and the bibliographies of selected studies were searched manually. The search was conducted independently by 2 authors. Study Selection: (1) any clinical trial, observational study or cross-sectional case series of 10 or more patients with a description of the conditions associated with bronchiectasis; (2) subjects aged 21 years or younger; (3) cystic fibrosis was excluded and; (4) the diagnosis was confirmed by computed tomography of the chest. Data Extraction: Patient number, age range, inclusion criteria, diagnostic criteria, patient source, and categorical and specific etiology. From 491 studies identified, 12 studies encompassing 989 children with non-CF bronchiectasis were selected. Sixty-three percent of the subjects had an underlying disorder. Infectious (17%), primary immunodeficiency (16%), aspiration (10%), ciliary dyskinesia (9%), congenital malformation (3%), and secondary immunodeficiency (3%) were the most common disease categories; 999 etiologies were identified. Severe pneumonia of bacterial or viral etiology and B cell defects were the most common disorders identified. The majority of children with non-CF bronchiectasis have an underlying disorder. A focused history and laboratory investigated is recommended.

Abstract: Background Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent irreversible dilatation and distortion of medium-sized bronchi. It has been suggested that with widespread use of high-resolution computed tomography, more bronchiectasis diagnoses are being made. Patients diagnosed with bronchiectasis frequently have difficulty expectorating sputum. Sputum therefore is retained in the lungs and may become infected, leading to further lung damage. Mucolytic agents target hypersecretion or changed physiochemical properties of sputum to make it easier to clear. One drug, recombinant human DNase, breaks down the DNA that is released at the site of infection by neutrophils. Mucus clearance along with antimicrobial therapy remains an integral part of bronchiectasis management. Chest physiotherapy along with mucolytic agents is commonly used in practice without clear supportive evidence. Objectives To determine whether ingested or inhaled mucolytics are effective in the treatment of patients with bronchiectasis. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of relevant articles. We contacted experts in the field and drug companies. Searches were current as of June 2013. Selection criteria Randomised trials of mucolytic treatment in people with bronchiectasis but not cystic fibrosis. Data collection and analysis Data extraction was performed independently by two review authors. Study authors were contacted for confirmation. Main results Four trials (with a combined total of 528 adult participants) were included, but almost none of the data from these studies could be aggregated in a meta-analysis. One trial (with 88 participants) compared bromhexine versus placebo. Compared with placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (mean difference (MD) -0.53, 95% confidence interval (CI) -0.81 to -0.25 at 16 days); the quality of the evidence was rated as low. A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16); again the quality of the evidence was rated as low. No significant differences between bromhexine and placebo were observed with respect to reported adverse events (odds ratio (OR) 2.93; 95% CI 0.12 to 73.97), and again the quality of the evidence was rated as low. In a single small, blinded but not placebo-controlled trial of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in forced expiratory volume in one second (FEV1) and 300 mL in forced vital capacity (FVC)) and was apparent only at day 15, not at earlier time points. The remaining two studies (with a combined total of 410 participants) compared recombinant human DNase (RhDNase) versus placebo. These two studies were very different (one was a two-week study of 61 participants, and the other ran for 24 weeks and included 349 participants), and the opportunity for combining data from the two studies was very limited. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. In all of the above comparisons of recombinant human DNase versus placebo, the quality of the evidence was judged to be low. Authors' conclusions Given the harmful effects of recombinant human DNase in one trial and no evidence of benefit, this drug should be avoided in non–cystic fibrosis bronchiectasis, except in the context of clinical trials. Evidence is insufficient to permit evaluation of the routine use of other mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance, but long-term data and robust clinical outcomes are lacking. Similarly, erdosteine may be a useful adjunct to physiotherapy in stable patients with mucus hypersecretion, but robust longer-term trials are required. Generally, clinical trials in children on the use of various mucolytic agents are lacking. As the number of agents available on the market, such as RhDNase, acetylcysteine and bromhexine, is increasing, improvement of the evidence base is needed.

Abstract: Sjogren syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic inflammation of exocrine glands and a variety of extraglandular sites. Lung involvement as defined by symptoms and either pulmonary function testing or radiographic abnormalities occurs in approximately 10 to 20% of patients. Subclinical lung disease is even more frequent and often includes evidence of small airways disease and airway inflammation. In general, patients will have evidence of both airway and interstitial lung disease by radiographs and pathology. Bronchiolitis and bronchiectasis are the most common airway manifestations while the interstitial pathologies associated with SS include nonspecific interstitial pneumonitis, usual interstitial pneumonitis, and lymphocytic interstitial pneumonitis. Patients with SS are also at an increased risk of lymphoma. A protean of other lung abnormalities including amyloidosis, granulomatous lung disease, pseudolymphoma, pulmonary hypertension, and pleural disease have been described.

Abstract: ObjectiveIndigenous children in developed countries are at increased risk of chronic suppurative lung disease (CSLD), including bronchiectasis. We evaluated sociodemographic and medical factors in indigenous children with CSLD/bronchiectasis from Australia, United States (US), and New Zealand (NZ).

Abstract: Background Bronchiectasis develops early in the course of cystic fibrosis, being detectable in infants as young as 10 weeks of age, and is persistent and progressive. We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) intensive surveillance program. Methods We examined data from 127 consecutive infants who received a diagnosis of cystic fibrosis after newborn screening. Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were performed, while the children were in stable clinical condition, at 3 months and 1, 2, and 3 years of age. Longitudinal data were used to determine risk factors associated with the detection of bronchiectasis from 3 months to 3 years of age. Results The point prevalence of bronchiectasis at each visit increased from 29.3% at 3 months of age to 61.5% at 3 years of age. In multivariate analyses, risk factors for bronchiectasis were presentation with meconium ileus (odds ratio, 3.17; 95% confidence interval [CI], 1.51 to 6.66; P = 0.002), respiratory symptoms at the time of CT and BAL (odds ratio, 2.27; 95% CI, 1.24 to 4.14; P = 0.008), free neutrophil elastase activity in BAL fluid (odds ratio, 3.02; 95% CI, 1.70 to 5.35; P<0.001), and gas trapping on expiratory CT (odds ratio, 2.05; 95% CI, 1.17 to 3.59; P = 0.01). Free neutrophil elastase activity in BAL fluid at 3 months of age was associated with persistent bronchiectasis (present on two or more sequential scans), with the odds seven times as high at 12 months of age and four times as high at 3 years of age. Conclusions Neutrophil elastase activity in BAL fluid in early life was associated with early bronchiectasis in children with cystic fibrosis. (Funded by the National Health and Medical Research Council of Australia and Cystic Fibrosis Foundation Therapeutics.)

Abstract: Primary immunodeficiencies (PID) are inherited disorders which one or several components of immune system are decreased or missing or of non-appropriate function. These diseases affect the development, function or morphology of the immune system. The group of primary immunodeficiencies comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. Their clinical presentation and complications depends on the type of defects and there is a great variability in the relationship between genotypes and phenotypes. A variation of clinical presentation across various age categories is also presented and children could widely differ from adult patients with PID. Respiratory symptoms and complications present a significant cause of morbidity and also mortality amongst patients suffering from different forms of PIDs and they are observed both in children and adults. They can affect primarily either upper airways (e.g. sinusitis, otitis media) or lower respiratory tract (e.g. pneumonia, bronchitis, bronchiectasis, interstitial lung diseases). The complications from lower respiratory tract are usually considered to be more important and also more specific for PIDs and they determinate patients’ prognosis. The spectrum of the causal pathogens usually demonstrates typical pattern characteristic for each PID category. The respiratory signs of PIDs can be divided into infectious (upper and lower respiratory tract infections and complications) and non-infectious (interstitial lung diseases, bronchial abnormalities – especially bronchiectasis, malignancies, benign lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at least slow down the development and course of respiratory complications of PIDs.

Abstract: We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as “adherent” to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies.

Abstract: Summary Ataxia–telangiectasia (A–T) is an autosomal recessive multiorgan disease characterized by progressive neurologic deterioration in which the most common causes of death are diseases of the respiratory system and cancer. This retrospective case-series characterizes the pulmonary disease seen in 101 cancer-free A–T patients who were living with chronic respiratory symptoms or who had pulmonary disease listed as the cause of their death. All of the 101 patients developed chronic progressive pulmonary disease with intermittent acute exacerbations and irreversible radiographic changes. Seventy-nine patients had microbiologic analysis of their respiratory secretions and of the patients less than 15 years of age, 25/27 cultured Staphylococcus aureus, Hemophilus influenzae, or Streptococcus pneumoniae and 35/47 older patients cultured Pseudomonas aeruginosa. Opportunistic infections of the lungs were not observed. Thirty-two patients had histologic examination of their lungs and 21 of the specimens had both acute and chronic inflammatory changes. The results of this study describe the natural history of the suppurative lung disease in patients with A–T that often progresses to bronchiectasis and pneumonias and ultimately respiratory failure. The etiology of the progressive deterioration is unknown but the pulmonary disease of A–T described in this study shows similarities to the lung disease seen in cystic fibrosis. Treatment of the lung disease in patients with A–T may benefit from many of the same therapies that have improved the quality of life for patients with cystic fibrosis. Pediatr Pulmonol. 2014; 49:389–399. © 2013 Wiley Periodicals, Inc.

Abstract: Rationale: The airways of people with cystic fibrosis (CF) are chronically infected with a variety of bacterial species. Although routine culture methods are usually used to diagnose these infections, culture-independent, DNA-based methods have identified many bacterial species in CF respiratory secretions that are not routinely cultured. Many prior culture-independent studies focused either on microbiota in explanted CF lungs, reflecting end-stage disease, or those in oropharyngeal swabs, which likely sample areas in addition to the lower airways. Therefore, it was unknown whether the lower airways of children with CF, well before end-stage but with symptomatic lung disease, truly contained diverse microbiota. Objectives: To define the microbiota in the diseased lung tissue of a child who underwent lobectomy for severe, localized CF lung disease. Methods: After pathologic examination verified that this child’s lung tissue reflected CF lung disease, we used bacterial ribosomal RNA gene pyrosequencing and computational phylogenetic analysis to identify the microbiota in serial sections of the tissue. Measurements and Main Results: This analysis identified diverse, and anatomically heterogeneous, bacterial populations in the lung tissue that contained both culturable and nonculturable species, including abundant Haemophilus, Ralstonia, and Propionibacterium species. Routine clinical cultures identified only Staphylococcus aureus, which represented only a small fraction of the microbiota found by sequencing. Microbiota analysis of an intraoperative oropharyngeal swab identified predominantly Streptococcus species. The oropharyngeal findings therefore represented the lung tissue microbiota poorly, in agreement with findings from earlier studies of oropharyngeal swabs in end-stage disease. Conclusions: These results support the concept that diverse and spatially heterogeneous microbiota, not necessarily dominated by “traditional CF pathogens,” are present in the airways of young, symptomatic children with early CF lung disease.

Abstract: Introduction Nontuberculous mycobacteria (NTM) have emerged as critical opportunistic pathogens of lung diseases recently. Patients with preexisting bronchiectasis are susceptible to NTM. Nevertheless, patients with preexisting bronchiectasis are susceptible to NTM but the prevalence of NTM pulmonary infection in different species and geographical areas is still not fully understood.

Abstract: Background Respiratory viral infections precipitate exacerbations of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease though similar data in non-cystic fibrosis (CF) bronchiectasis are missing. Our study aimed to determine the point prevalence of viruses associated with exacerbations and evaluate clinical and investigational differences between virus-positive and -negative exacerbations in children with bronchiectasis. Methods A cohort of 69 children (median age 7 years) with non-CF bronchiectasis was prospectively followed for 900 child-months. PCR for 16 respiratory viruses was performed on nasopharyngeal aspirates collected during 77 paediatric pulmonologist-defined exacerbations. Clinical data, systemic (C reactive protein (CRP), IL-6, procalcitonin, amyloid-A, fibrinogen) and lung function parameters were also collected. Findings Respiratory viruses were detected during 37 (48%) exacerbations: human rhinovirus (HRV) in 20; an enterovirus or bocavirus in four each; adenoviruses, metapneumovirus, influenza A virus, respiratory syncytial virus, parainfluenza virus 3 or 4 in two each; coronavirus or parainfluenza virus 1 and 2 in one each. Viral codetections occurred in 6 (8%) exacerbations. HRV-As (n=9) were more likely to be present than HRV-Cs (n=2). Children with virus-positive exacerbations were more likely to require hospitalisation (59% vs 32.5% (p=0.02)) and have fever (OR 3.1, 95% CI 1.2 to 11.1), hypoxia (OR 25.5, 95% CI 2.0 to 322.6), chest signs (OR 3.3, 95% CI 1.1 to 10.2) and raised CRP (OR 4.7, 95% CI 1.7 to 13.1) when compared with virus-negative exacerbations. Interpretation Respiratory viruses are commonly detected during pulmonary exacerbations of children with bronchiectasis. HRV-As were the most frequently detected viruses with viral codetection being rare. Time-sequenced cohort studies are needed to determine the role of viral–bacterial interactions in exacerbations of bronchiectasis.

Abstract: Background and objective Reliable markers of disease progression or stability to assist in management decisions are lacking in patients with non-cystic fibrosis bronchiectasis and Mycobacterium avium complex (MAC) infection. Methods Data from 52 adults with non-cystic fibrosis bronchiectasis and coexisting MAC infection managed at our institution over a 5-year period were retrospectively analysed. High-resolution computed tomography (HRCT) scans were scored using a scoring system that focused on findings associated with MAC infection. Results Chronic pulmonary aspergillosis was independently associated with mortality (hazard ratio (HR) = 8.916, 95% confidence interval (CI) = 1.324–60.027), as were nodules with cavitation (HR = 5.911, 95% CI = 1.095–25.911) and emphysema (HR = 1.027, 95% CI = 1.002–1.053) on HRCT. Anti-MAC chemotherapy was more likely to lead to MAC culture conversion (67% vs 27%, P = 0.005) but did not improve survival as compared with patients managed with observation. Longitudinally, patients who had improvements in HRCT scores were younger (60.2 ± 9.19 years vs 69.83 ± 12.43 years, P = 0.043), while the presence of cavitation within nodules predicted a deterioration in HRCT scores (0.5 (0–3) vs 0 (0–1), P = 0.033). No significant longitudinal differences were found in lung function in the cohort as a whole or within different groups. Conclusions Chronic pulmonary aspergillosis in patients with bronchiectasis and coexisting MAC infection is a strong predictor of mortality. Cavitation within nodules and emphysema on HRCT at presentation were independently associated with mortality.

Abstract: Background Characteristics of lung function impairment in bronchiectasis is not fully understood. Objectives To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). Methods We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. Results In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46–15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52–15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21–18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20–17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Conclusion Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. Trial Registration ClinicalTrials.gov NCT01761214

Abstract: Crohn's disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.

Abstract: Background Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients. Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation. Objectives To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis. Search methods We searched the Cochrane Airways Group Specialised Register, trials registries, and the reference lists of included studies and review articles. Searches are current up to April 2014. Selection criteria Any randomised controlled trial (RCT) using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis. Data collection and analysis Two review authors assessed studies for suitability. We used standard methods recommended by The Cochrane Collaboration. Main results Eleven studies met the inclusion criteria of the review (1021 participants). Five studies on 833 participants compared inhaled mannitol with placebo but poor outcome reporting meant we could pool very little data and most outcomes were reported by only one study. One 12-month trial on 461 participants provided results for exacerbations and demonstrated an advantage for mannitol in terms of time to first exacerbation (median time to exacerbation 165 versus 124 days for mannitol and placebo respectively (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63 to 0.96, P = 0.022) and number of days on antibiotics for bronchiectasis exacerbations was significantly better with mannitol (risk ratio (RR) 0.76, 95%CI 0.58 to 1.00, P = 0.0496). However, exacerbation rate per year was not significantly different between mannitol and placebo (RR 0.92 95% CI 0.78 to 1.08). The quality of this evidence was rated as moderate. There was also an indication, from only three trials, again based on moderate quality evidence, that mannitol improves health-related quality of life (mean difference (MD) -2.05; 95% CI -3.69 to -0.40). An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo (OR 0.96; 95% CI 0.61 to 1.51). Two additional small trials on 25 participants compared mannitol versus no treatment and the data from these studies were inconclusive. Four studies (combined N = 113) compared hypertonic saline versus isotonic saline. On most outcomes there were conflicting results and the opportunities for the statistical aggregation of data from studies was very limited. It is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available. Authors' conclusions There is an indication from a single, large, unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis. In patients with near normal lung function, spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo. Further investigation is required in a patient population with impaired lung function. It is not possible to draw firm conclusions regarding the effect of nebulised hypertonic saline due to significant differences in the methodology, patient groups, and findings amongst the limited data available. The data suggest that it is unlikely to have benefit over isotonic saline in patients with milder disease, and hence future studies should test its use in those with more severe disease Plain language summary Inhaled hyperosmolar agents for bronchiectasis Review question We wanted to know if inhaled hyperosmolar agents - treatments which help people cough up sputum - may be helpful for people with bronchiectasis. We only included trials on people who had bronchiectasis and who did not have cystic fibrosis. Therefore we are unable to draw any conclusions for people with cystic fibrosis. Background Bronchiectasis is a lung condition that usually develops after a series of lung problems (such as childhood infections, problems in the lung structure, tuberculosis, and cystic fibrosis). A lot of mucus (phlegm) collects in the lungs, causing discomfort and the need to cough it up. The phlegm also collects bacteria, which can add to breathing difficulties and make people very ill by causing recurring lung infections that are difficult to clear with antibiotics. Breathing in (inhaling) hypertonic saline (salt solutions with a greater salt content than blood) liquids may help clear this mucus, as may the drug mannitol (inhaled in dry powder form). This is because the concentrated salt or sugar (mannitol) draws water into the mucus in the lung and makes it thinner and easier to cough out. Study characteristics We found 11 randomised controlled trials on 1021 participants that compared inhaled hyperosmolar agents versus no mucolytic treatment. Five studies compared inhaled mannitol versus placebo (with a total of 883 participants) and two very small studies (with a total of just 25 participants) compared inhaled mannitol with no treatment. We also found four studies (with a total of 113 participants) that compared hypertonic saline with isotonic (normal) saline. Key results For the comparison between mannitol and placebo only one study (a 12-month trial with 461 participants) provided information on the number of people who had an exacerbation (or flare up) over the course of a year. This study showed that people who were treated with mannitol had 8% fewer exacerbations on average compared with placebo. Overall, we felt the quality of this evidence was moderate and new trials would be likely to change either how effective we think the treatment is or how confident we are about it. Three trials assessed the effect of mannitol on health-related quality of life, and again the quality of the evidence was rated as moderate. An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo The trials comparing hypertonic saline with isotonic saline had conflicting results for most of the outcomes of interest. Because we were unable to combine the data, it is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available. Our analysis of adverse events between hypertonic saline versus isotonic saline showed no significant difference however this was based on a single study and the quality of the evidence was moderate. Quality of the evidence Details of how the patients in the trials were allocated to receive mannitol or not was clearly described in only one of the studies, and similarly only one of the hypertonic saline versus isotonic saline studies provided this information. The general lack of information on this point was considered carefully in the review in relation to our level of uncertainty in interpreting the results. Taking this into account, the quality of evidence was generally regarded as moderate both for the mannitol and hypertonic saline studies.

Abstract: Background A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis.

Abstract: Despite our current treatment, many cystic fibrosis (CF) patients still show progressive bronchiectasis and small airways disease. Adequate detection and monitoring of progression of these structural abnormalities is needed to personalize treatment to the severity of CF lung disease of the patient. Chest computed tomography (CT) is the gold standard to diagnose and monitor bronchiectasis. Many studies have been done to validate the role of chest CT in CF and to improve the protocols. From these studies it became clear that for correct interpretation of the severity of bronchiectasis and small airways disease standardization of lung volume for the inspiratory and expiratory CT scan acquisition is needed. The risk related to the radiation exposure of a chest CT scan every second year is considered low. Automated and quantitative image analysis systems are developed to improve the reliability and sensitivity of assessments of structural lung changes in CF, particularly in early life. In this paper an overview is given of the lessons learned from two decades of monitoring CF lung disease using chest CT.

Abstract: Background: Bronchiectasis and asthma are different in many respects, but some patients have both conditions. Studies assessing the effect of bronchiectasis on asthma exacerbation are rare. The aim of this study is to investigate the effect of bronchiectasis on asthma exacerbation. Methods: We enrolled 2,270 asthma patients who were followed up in our hospital. Fifty patients had bronchiectasis and asthma. We selected fifty age- and sex-matched controls from the 2,220 asthma patients without bronchiectasis, and assessed asthma exacerbation and its severity based on the annual incidence of total asthma exacerbation, annual prevalence of steroid use, and frequency of emergency room visits and hospitalizations due to asthma exacerbation in each group. Results: Fifty patients (2.2%) had bronchiectasis and asthma. The annual incidence of asthma exacerbation was higher in patients with asthma and bronchiectasis than in patients with asthma alone (1.08±1.68 vs. 0.35±0.42, p=0.004). The annual prevalence of steroid use (0.9±1.54 vs. 0.26±0.36, p=0.006) and the frequency of emergency room visits (0.46±0.84 vs. 0.02±0.13, p=0.001) due to asthma exacerbation were also higher in patients with asthma and bronchiectasis than in patients with asthma alone. Conclusion: Bronchiectasis is associated with difficult asthma control.

Abstract: Free to read BACKGROUND Bronchiectasis is a major contributor to chronic respiratory morbidity and mortality worldwide. Wheeze and other asthma-like symptoms and bronchial hyperreactivity may occur in people with bronchiectasis. Physicians often use asthma treatments in patients with bronchiectasis. OBJECTIVES To assess the effects of inhaled long-acting beta2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (1) acute exacerbations and (2) stable state. SEARCH METHODS The Cochrane Airways Group searched the the Cochrane Airways Group Specialised Register of Trials, which includes records identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other databases. The Cochrane Airways Group performed the latest searches in October 2013. SELECTION CRITERIA All randomised controlled trials (RCTs) of combined ICS and LABA compared with a control (placebo, no treatment, ICS as monotherapy) in children and adults with bronchiectasis not related to cystic fibrosis (CF). DATA COLLECTION AND ANALYSIS Two review authors extracted data independently using standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS We found no RCTs comparing ICS and LABA combination with either placebo or usual care. We included one RCT that compared combined ICS and LABA with high-dose ICS in 40 adults with non-CF bronchiectasis without co-existent asthma. All participants received three months of high-dose budesonide dipropionate treatment (1600 micrograms). After three months, participants were randomly assigned to receive either high-dose budesonide dipropionate (1600 micrograms per day) or a combination of budesonide with formoterol (640 micrograms of budesonide and 18 micrograms of formoterol) for three months. The study was not blinded. We assessed it to be an RCT with overall high risk of bias. Data analysed in this review showed that those who received combined ICS-LABA (in stable state) had a significantly better transition dyspnoea index (mean difference (MD) 1.29, 95% confidence interval (CI) 0.40 to 2.18) and cough-free days (MD 12.30, 95% CI 2.38 to 22.2) compared with those receiving ICS after three months of treatment. No significant difference was noted between groups in quality of life (MD -4.57, 95% CI -12.38 to 3.24), number of hospitalisations (odds ratio (OR) 0.26, 95% CI 0.02 to 2.79) or lung function (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)). Investigators reported 37 adverse events in the ICS group versus 12 events in the ICS-LABA group but did not mention the number of individuals experiencing adverse events. Hence differences between groups were not included in the analyses. We assessed the overall evidence to be low quality. AUTHORS' CONCLUSIONS In adults with bronchiectasis without co-existent asthma, during stable state, a small single trial with a high risk of bias suggests that combined ICS-LABA may improve dyspnoea and increase cough-free days in comparison with high-dose ICS. No data are provided for or against, the use of combined ICS-LABA in adults with bronchiectasis during an acute exacerbation, or in children with bronchiectasis in a stable or acute state. The absence of high quality evidence means that decisions to use or discontinue combined ICS-LABA in people with bronchiectasis may need to take account of the presence or absence of co-existing airway hyper-responsiveness and consideration of adverse events associated with combined ICS-LABA.

Abstract: Wet cough is a common feature of many disease processes affecting children. Our aim was to examine the relationships between cough nature, lower airway infection (bacterial, viral, and viral-bacterial) and severity of neutrophilic airway inflammation. We hypothesized that viral-bacterial co-infection of the lower airway would be associated with wet cough and heightened neutrophilic airway inflammation. We prospectively recruited 232 children undergoing elective flexible bronchoscopy. Participants were grouped using a cough nature symptom-based approach, into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature, and duration of cough and key demographic factors, were collected. Children with wet cough (n = 143) were more likely to have lower airway bacterial infection (OR 2.6, P = 0.001), viral infection (OR 2.04, P = 0.045) and viral-bacterial co-infection (OR 2.65, P = 0.042) compared to those without wet cough. Wet cough was associated with heightened airway neutrophilia (median 19%) as compared to dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18%, and 6%, respectively, P < 0.0001). Children with wet cough had higher rates of lower airway infection with bacteria and viruses. Maximal neutrophilic airway inflammation was seen in those with viral-bacterial co-infection. Cough nature may be a useful indicator of infection and inflammation of the lower airways in children.

Abstract: Early diagnosis and treatment of nontuberculous mycobacterial lung diseases (NTM-LD) and pulmonary tuberculosis (PTB) are important clinical issues. The present study aimed to compare and identify the chest CT characteristics that help to distinguish NTM lung disease from PTB in patients with acid-fast bacilli (AFB) smear-positive sputum. From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained from the 159 patients were analyzed, 75 scans were from patients with PTB and 20 scans from NTM-LD. The typical chest CT findings of mycobacterial diseases were analyzed. In patients with PTB, the prevalence of pleural effusion (38.7% vs. 15.0%; P =0.047), nodules < 10 mm in size (76.0% vs. 25.0%; P < 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P =0.021), and cavities (31.1% vs. 5.0%; P =0.018) were significantly higher than patients with NTM. Of the 20 patients with NTM lung diseases, bronchiectasis and cystic changes were significantly higher than patients with PTB (20.0% vs. 4.0%; P = 0.034). In multivariate analysis, CT scan findings of nodules was independently associated with patients with diagnoses of PTB (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02-0.30). Presence of bronchiectasis and cystic changes in CT scans was strongly associated with patients with NTM-LD (OR, 33.04; 95% CI, 3.01-362.55). The CT distinction between NTM-LD and PTB may help radiologists and physicians to know the most likely diagnoses in AFB-smear positive patients and avoid unnecessary adverse effects and the related costs of anti-TB drugs in endemic areas.

Abstract: Introduction: Allergic bronchopulmonary aspergillosis (ABPA) is a progressive disease which can lead to recurrent exacerbations, bronchiectatic changes and end-stage fibrosis. Early diagnosis and treatment prevents its progression and alleviate its clinical manifestations. High resolution CT of the chest has emerged as a promising investigation for its diagnosis. Aims and Objectives:To review the high resolution computed tomography (HRCT) chest manifestations in ABPA patients. Materials and Methods:This study included 110 patients with ABPA who had undergone HRCT of the chest in the routine diagnostic workup for ABPA. The scans were assessed for changes in bronchi, parenchyma and pleura and findings consistent with ABPA were evaluated. Results: HRCT chest was normal in 24 patients. 86 patients demonstrated central bronchiectasis with predilection for upper and middle lobes. Centrilobular nodules with or without linear opacities (tree in bud pattern), mucoceles and high-attenuation mucus were seen in 86%, 59% and 36% patients respectively. Conclusion: Central bonchiectasis combined with centrilobular nodules and mucus impaction (especially high attenuation mucus) strongly favour the diagnosis of ABPA.