Two Japanese Pediatric Patients With Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in the CCNO gene.

Primary ciliary dyskinesia (PCD) is a rare congenital disorder caused by pathogenic variants of genes related to cilia. Here, we report two Japanese pediatric patients with PCD caused by pathogenic compound heterozygous variants in the cyclin O (CCNO) gene (Case 1, NM_021147.4:c.[262C>T];[781delC], p.[Gln88Ter];[Leu261fs]; Case 2, c.[262C>T];[c.248_252dupTGCCC], p.[Gln88Ter];[Gly85fs]). The clinical symptoms of the patients were varied. Neither of the patients had situs inversus. Transmission electron microscopy of the respiratory cilia from the nasal mucosa in Case 1 showed a remarkable reduction of cilia and the few residual cilia had central pair defects and microtubular disorganization.

Efectividad del tratamiento con ciprofloxacino durante 21 días en la primoinfección por pseudomonas aeruginosa en las bronquiectasias no fibrosis quística / Effectiveness of treatment with ciprofloxacin during 21 days in primoinfection by pseudomonas aeruginosa in the bronchiectasia not cystic fibrosis

Las bronquiectasias no debidas a fibrosis quística (FQ) constituyen la tercera patología inflamatoria crónica más frecuente de las vías respiratorias.La infección bronquial determina la progresión de la enfermedad, siendo la infección por Pseudomonas aeruginosa la que se asocia con peor pronóstico. Por este motivo, las guías de práctica clínica recomiendan la erradicación de P. aeruginosa en la infección primaria. Hasta el momento ningún estudio ha demostrado la utilidad real de esta pauta de tratamiento en el manejo de la infección bronquial inicial por Pseudomonas aeruginosa, por lo que el objetivo de este estudio es determinar la efectividad del tratamiento con Ciprofloxacino 750 mg cada 12 horas por vía oral durante 21 días en la erradicación de P. aeruginosa en pacientes con bronquiectasias no relacionadas con FQ. (AU)

Bronchiectasis not due to cystic fibrosis (CF) constitutes the third most frequent chronic inflammatory pathology of the airways. Bronchial infection determines the progression of the disease, being infection by Pseudomonas aeruginosa the one that is associated with the worst prognosis. For this reason, clinical practice guidelinesrecommend eradication of P. aeruginosa in primary infection. At the moment, any study has shown the real usefulness of this treatment regimen in the management of the initial bronchial infection by Pseudomonas aeruginosa, so the objective of this study is to determine the effectiveness of treatment with Ciprofloxacin 750 mg every 12 hours orally for 21 days in the eradication of P. aeruginosa in patients with non-CF bronchiectasis. (AU)

Frequency of Obstructive Sleep Apnea in Patients With Cystic Fibrosis and Non-cystic Fibrosis Bronchiectasis and Its Association With Clinical Findings.

OBJECTIVE: This study was designed to assess obstructive sleep apnea (OSA) in adult patients with cystic fibrosis (CF) and non-CF bronchiectasis (BE) and to relate it with clinical characteristics. METHODS: Thirty-five CF (27 years) and 35 non-CF (24 years) BE patients were included. Demographic characteristics, medications, comorbidities, BMI, dyspnea scales, pulmonary functions, sputum cultures, exacerbations, and hospitalizations were recorded. The Epworth Sleepiness Scale (ESS) questionnaire was filled and polysomnography was performed for each patient. RESULTS: ESS scores did not show any significant difference between CF and non-CF BE patients. Thirty-seven (53%) of all patients had OSA. There was no significant difference in OSA risk between CF and non-CF BE patients (54% vs 51%, respectively). Male gender was found to be a risk factor for OSA (68% of males vs 41% of females, respectively, p:0.026). Total sleep time, sleep efficiency, sleep latency, time spent awake after falling asleep, oxygen desaturation index, apnea-hypopnea-index (AHI), AHI in the supine position, and rapid eye movement phase did not show any significant difference between CF and non-CF patients. CF patients had significantly lower mean oxygen saturation (p:0.001) and lowest oxygen saturation (p:0.0024) levels and higher heart rate (p:0.02) compared to non-CF BE patients. Multiple logistic regression analysis of all patients revealed male gender and disease duration as risk factors for OSA (p:0.023 and p:0.041 respectively). CONCLUSION: It is remarkable that more than half of the patients in both CF and non-CF bronchiectasis groups had OSA. Male gender and disease duration were found as risk factors for OSA.

Whole-Body Vibration or Aerobic Exercise in Patients with Bronchiectasis? A Randomized Controlled Study.

Background and Objectives: The whole-body vibration (WBV) technique is an exercise training method. It has been reported to improve muscle strength, exercise capacity, and the quality of life. However, there is no study on the use of the WBV technique in bronchiectasis. The aim of the present study is to compare the effect of aerobic exercise with whole-body vibration on exercise capacity, respiratory function, dyspnea, and quality of life (QoL) in bronchiectasis patients. Materials and Methods: Clinically stable bronchiectasis patients aged 18−74 years participated in this study. A pulmonary function test, 6 minute walk test (6MWT), five times sit-to-stand test (FTSST), Modified Medical Research Council (mMRC) Scale, an, St. Georges Respiratory Questionnaire (SGRQ) were used in the evaluation. In total, 41 patients (WBV group: 20, aerobic group: 21) completed the study. The patients were treated for eight weeks. Results: When the two groups were compared after the treatment, there was a significant difference between the mMRC scores in favor of the WBV group (p < 0.05). When the results of the WBV group were examined before and after treatment, a significant difference was found between the 5SST and 6MWT (p < 0.05). When the aerobic group was compared before and after the treatment, it was observed that there was a significant difference in FVC, FVC%, 5SST, 6MWT, and SGRQ total score, and activity and impact scores, which are the sub-parameters (p < 0.05). Conclusions: Eight weeks of WBV exercise can lead to significant improvements in patients with bronchiectasis, exercise capacity, and dyspnea. Larger studies are needed to define the optimal intensity and duration of WBV, as well as to investigate its possible long-term effects.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Rheology predicts sputum eosinophilia in patients with muco-obstructive lung diseases.

BACKGROUND: Mucus is known to play a pathogenic role in muco-obstructive lung diseases, but little is known about the determinants of mucus rheology. The purpose of this study is to determine which sputum components influence sputum rheology in patients with muco-obstructive lung diseases. METHODS: We performed a cross sectional prospective cohort study. Spontaneous sputum was collected from consecutive patients with muco-obstructive lung diseases. Sputum rheology was assessed using the Rheomuco® rheometer (Rheonova, Grenoble); the elastic modulus G', viscous modulus G″, and the critical stress threshold σc were recorded. Key quantitative and qualitative biological sputum components were determined by cytology, nucleic acid amplification tests and mass spectrometry. RESULTS: 48 patients were included from January to August 2019. Among them, 10 had asthma, 14 COPD and 24 non-CF bronchiectasis (NCFB). The critical stress threshold σc predicted a sputum eosinophilia superior to 1.25% with 89.19% accuracy (AUC = 0.8762). G' and G″ are positively correlated with MUC5AC protein concentration ((rho = 0.361; P = .013) and (rho = 0.335; P = .021), respectively). σc was positively correlated with sputum eosinophilia (rho = 0.394; P = .012), MUC5B (rho = 0.552; P < .001) and total protein (rho = 0.490; P < .001) concentrations. G' and G″ were significantly higher in asthma patients (G' = 14.49[7.18-25.26]Pa, G'' = 3.0[2.16-5.38]Pa) compared to COPD (G' = 5.01[2.94-6.48]Pa, P = .010; G'' = 1.45[1.16-1.94]Pa, P = .006) and to NCFB (G' = 4.99[1.49-10.49]Pa, P = .003; G'' = 1.46[0.71-2.47]Pa, P = .002). CONCLUSION: In muco-obstructive lung diseases, rheology predicts sputum eosinophilia and is correlated with mucin concentrations, regardless of the underlying disease. CLINICAL TRIAL REGISTRATION: (registrar, website, and registration number), where applicable NCT04081740.

Sputum neutrophil elastase and its relation to pediatric bronchiectasis severity: A cross-sectional study.

Background and Aims: Sputum neutrophil elastase (NE) is a marker of neutrophilic airway inflammation in bronchiectasis. Yet, not much is known about its role in pediatric bronchiectasis severity. This study aimed to assess the sputum NE value as a biomarker of clinical and radiological severity in pediatric bronchiectasis. Methods: This was a cross-sectional study assessing sputum NE in a total of 50 bronchiectasis patients under the age of 18 years-30 patients with cystic fibrosis (CF) and 20 patients with non-CF bronchiectasis were included. Bronchiectasis severity was assessed using Shwachman-Kulczycki (SK) score, CF-ABLE score, and CF risk of disease progression score, among CF patients, and bronchiectasis severity index (BSI) and FACED criteria among non-CF bronchiectasis patients, associations between sputum NE and bronchiectasis severity were assessed in both patient groups. Results: Sputum NE was directly correlated with C-reactive protein (r = 0.914, p < 0.001), (r = 0.786, p < 0.001), frequency of exacerbations (r = 0.852, p < 0.001) (r = 0.858, p < 0.001), exacerbations severity (r = 0.735, p = 0.002), (r = 0.907, p < 0.001), and the number of hospital admissions (r = 0.813, p < 0.001), (r = 0.612, p =0.004) in the last year among CF, and non-CF bronchiectasis patients, respectively. Additional linear correlations were found between sputum NE, CF risk of disease progression score (p < 0.001), CF-ABLE score (p < 0.001), and lower forced expiratory volume 1% of predicted (p = 0.017; ρ = -0.8) among CF patients. Moreover, sputum NE was positively correlated with the neutrophil count (p = 0.018), and BSI severity score (p = 0.039; ρ = 0.465) among non-CF bronchiectasis patients. Conclusions: Sputum NE may be considered a good biomarker of bronchiectasis severity in both CF and non-CF bronchiectasis patients, as confirmed by the exacerbations rate, CF risk of disease progression, and BSI scores.

Carriage and Transmission of Macrolide Resistance Genes in Patients With Chronic Respiratory Conditions and Their Close Contacts.

BACKGROUND: Long-term macrolide therapy has been shown to provide benefit to those with a range of chronic respiratory conditions. However, concerns remain about the impact of macrolide exposure on the carriage and abundance of antibiotic resistance genes within the oropharynx. The potential for onward transmission of resistance from macrolide recipients to their close contacts also is poorly understood. RESEARCH QUESTION: Does long-term macrolide use impact carriage of resistance within the oropharyngeal microbiota in people with chronic respiratory conditions and risk of onward transmission to their close contacts? STUDY DESIGN AND METHODS: Oropharyngeal swabs were collected from 93 individuals with chronic respiratory conditions, 53 of whom were receiving long-term macrolide therapy. An oropharyngeal swab also was collected from a close cohabiting contact of each patient. Detection and abundance of 10 macrolide-associated resistance genes with the potential to disseminate via horizontal gene transfer were assessed by quantitative polymerase chain reaction analysis. RESULTS: Detection of resistance genes in macrolide recipients was comparable with that in nonrecipients. However, the normalized gene abundance of erm(B) was significantly higher in the macrolide recipient group (P = .045). Among the close contacts, no between-group differences in resistance gene detection or abundance were identified. Within-group analysis showed that the detection of erm(F) and mef in macrolide recipients, but not nonrecipients, was associated significantly with detection in close contacts (P = .003 and P = .004, respectively). However, between-group analysis showed that treatment group did not predict cocarriage between patients and their close contacts (P > .05 for each gene). INTERPRETATION: Although levels of erm(B) were higher in those receiving long-term macrolide therapy and evidence of gene cocarriage with close contacts was found, no evidence was found that macrolide use increased the onward transmission risk to their close contacts. This study therefore addresses concerns that long-term macrolide therapy could promote the dissemination of transmissible macrolide resistance.

Surgical treatment of non-cystic fibrosis bronchiectasis in Central Europe.

BACKGROUND: Bronchiectasis is a mostly irreversible bronchial dilatation induced by the destruction of elastic and muscular fibers of the bronchial wall. Surgical treatment is usually reserved for focal disease, and whenever complications, like hemoptysis or secondary aspergilloma, arise. In this study, we report our experience and outcomes in surgical bronchiectasis management between 2016 and 2020. METHODS: We retrospectively searched our database for patients admitted for surgical treatment of bronchiectasis between 2016 and 2020. All records were screened for pre-surgical management. Age, gender, distribution of bronchiectatic lesions, type of surgery, perioperative complications, chest tube duration, length of hospital stay as well as 30-day-mortality were recorded, and a brief follow-up was made. RESULTS: A total of n=34 patients underwent pulmonary resection with bronchiectasis. Mean age on admission was 56.2±15.1 years and n=21 patients (62%) were female. In n=23 cases the right lung was affected, in n=9 cases the left side and in two cases both lungs. Indications for surgery included persistent major alterations after conservative therapy (n=9), massive hemoptysis (n=4), and full-blown "destroyed lobe" (n=7). All patients received anatomical lung resection (n=21 lobectomies, n=2 bilobectomies and n=11 segmentectomies), either by uniportal video assisted thoracoscopic surgery (n=28) or by lateral thoracotomy (n=6). Average length of hospital stay was 7.9±6.3 days; one patient died on POD 7 due to myocardial infarction. CONCLUSIONS: In spite of a decreasing number of patients with bronchiectasis referred to surgery due to improvements in preventing and managing the disease, pulmonary resection still plays a significant role in treating this pathology in Central Europe. Surgery remains a viable approach for localized forms of bronchiectasis, and the only option in treating acute deterioration and complications like massive hemoptysis.

Do Redox Balance and Inflammatory Events Take Place in Mild Bronchiectasis? A Hint to Clinical Implications.

We hypothesized that in mild bronchiectasis patients, increased systemic inflammation and redox imbalance may take place and correlate with clinical parameters. In plasma samples from patients with very mild bronchiectasis, inflammatory cells and molecules and redox balance parameters were analyzed. In the patients, lung function and exercise capacity, nutritional status, bacterial colonization, and radiological extension were assessed. Correlations between biological and clinical variables were determined. Compared to healthy controls, levels of acute phase reactants, neutrophils, IgG, IgA, myeloperoxidase, protein oxidation, and GSH increased and lung function and exercise capacity were mildly reduced. GSH levels were even greater in ex-smoker and Pseudomona-colonized patients. Furthermore, radiological extension inversely correlated with airway obstruction and, disease severity, and positively correlated with neutrophil numbers in mild bronchiectasis patients with no nutritional abnormalities. In stable patients with mild bronchiectasis, several important inflammatory and oxidative stress events take place in plasma. These findings suggest that the extension of bronchiectasis probably plays a role in the development of redox imbalance and systemic inflammation in patients with mild bronchiectasis. These results have therapeutic implications in the management of bronchiectasis patients.

Whole genome sequencing in the diagnosis of primary ciliary dyskinesia.

BACKGROUND: It is estimated that 1-13% of cases of bronchiectasis in adults globally are attributable to primary ciliary dyskinesia (PCD) but many adult patients with bronchiectasis have not been investigated for PCD. PCD is a disorder caused by mutations in genes required for motile cilium structure or function, resulting in impaired mucociliary clearance. Symptoms appear in infancy but diagnosis is often late or missed, often due to the lack of a "gold standard" diagnostic tool and non-specific symptoms. Mutations in > 50 genes account for around 70% of cases, with additional genes, and non-coding, synonymous, missense changes or structural variants (SVs) in known genes presumed to account for the missing heritability. METHODS: UK patients with no identified genetic confirmation for the cause of their PCD or bronchiectasis were eligible for whole genome sequencing (WGS) in the Genomics England Ltd 100,000 Genomes Project. 21 PCD probands and 52 non-cystic fibrosis (CF) bronchiectasis probands were recruited in Wessex Genome Medicine Centre (GMC). We carried out analysis of single nucleotide variants (SNVs) and SVs in all families recruited in Wessex GMC. RESULTS: 16/21 probands in the PCD cohort received confirmed (n = 9), probable (n = 4) or possible (n = 3) diagnosis from WGS, although 13/16 of these could have been picked up by current standard of care gene panel testing. In the other cases, SVs were identified which were missed by panel testing. We identified variants in novel PCD candidate genes (IFT140 and PLK4) in 2 probands in the PCD cohort. 3/52 probands in the non-CF bronchiectasis cohort received a confirmed (n = 2) or possible (n = 1) diagnosis of PCD. We identified variants in novel PCD candidate genes (CFAP53 and CEP164) in 2 further probands in the non-CF bronchiectasis cohort. CONCLUSIONS: Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.

Recurrent Lower Respiratory Tract Infections Due to Mounier-Kuhn Syndrome.

Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by recurrent lower respiratory tract infections and bronchiectasis due to dilation of the trachea and bronchi. Diagnosis is made based on clinical suspicion along with radiographic evidence of tracheobronchomegaly. Mucolytic agents and chest physiotherapy have been shown to offer symptomatic improvement, and definitive surgical treatment is reserved for those with persistent symptoms. Herein, we report a case of MKS in a 72-year-old woman with bronchiectasis and recurrent multidrug-resistant lower respiratory tract infections.

Allergic Bronchopulmonary Aspergillosis With or Without Asthmatic Symptoms?

Allergic bronchopulmonary aspergillosis (ABPA) is a localized inflammatory airway disease seen in patients sensitized to Aspergillus fumigatus (A. fumigatus) antigens. The disease presents with productive cough, wheezing, episodic fever, as well as central bronchiectasis (CB) and mucus plugs on computed tomography (CT) scans. If treated accordingly, symptoms and pulmonary damage caused by ABPA can be reverted. Currently, the diagnostic criteria for ABPA require the diagnosis of predisposing pulmonary diseases such as asthma and cystic fibrosis (CF) in order to establish the diagnosis. There has been an increasing number of cases reporting ABPA without evidence of past asthmatic history or symptoms. This reflects the need for more sensitive diagnostic tests in order to prevent progression to irreversible lung injury. Here we report a 22-year-old Puerto Rican male who went undiagnosed for ABPA for 12 months due to the absence of asthma or CF history.

Pseudomonas aeruginosa infection, but not mono or dual-combination CFTR modulator therapy affects circulating regulatory T cells in an adult population with cystic fibrosis.

BACKGROUND: Chronic infection and an exaggerated inflammatory response are key drivers of the pathogenesis of cystic fibrosis (CF), especially CF lung disease. An imbalance of pro- and anti-inflammatory mediators, including dysregulated Th2/Th17 cells and impairment of regulatory T cells (Tregs), maintain CF inflammation. CF transmembrane conductance regulator (CFTR) modulator therapy might influence these immune cell abnormalities. METHODS: Peripheral blood mononuclear cells and serum samples were collected from 108 patients with CF (PWCF) and 40 patients with non-CF bronchiectasis. Samples were analysed for peripheral blood lymphocytes subsets (Tregs; Th1-, Th1/17-, Th17- and Th2-effector cells) and systemic T helper cell-associated cytokines (interleukin [IL]-5, IL-13, IL-2, IL-6, IL-9, IL-10, IL-17A, IL-17F, IL-4, IL-22, interferon-γ, tumour necrosis factor-α) using flow cytometry. RESULTS: 51% of PWCF received CFTR modulators (ivacaftor, ivacaftor/ lumacaftor or tezacaftor/ ivacaftor). There were no differences in proportions of analysed T cell subsets or cytokines between PWCF who were versus were not receiving CFTR modulators. Additional analysis revealed lower percentages of Tregs in PWCF and chronic pulmonary Pseudomonas aeruginosa infection; this difference was also present in PWCF treated with CFTR modulators. Patients with non-CF bronchiectasis tended to have higher percentages of Th2- and Th17-cells and higher levels of peripheral cytokines versus PWCF. CONCLUSIONS: Chronic P. aeruginosa lung infection appears to impair Tregs in PWCF (independent of CFTR modulator therapy) but not those with non-CF bronchiectasis. Moreover, our data showed no statistically significant differences in major subsets of peripheral lymphocytes and cytokines among PWCF who were versus were not receiving CFTR modulators.

Comparison of respiratory pathogen colonization and antimicrobial susceptibility in people with cystic fibrosis bronchiectasis versus non-cystic fibrosis bronchiectasis: a protocol for a systematic review.

BACKGROUND: Both cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis are characterized by permanent bronchial dilation, impaired mucociliary clearance, and development of chronic colonization and infection. Although the major airway microbiota in both CF and non-CF bronchiectasis may be similar, there are some differences in clinical and microbiologic features. There may also be differences in antibiotic susceptibility patterns between the CF and non-CF populations. Therefore, analysis and comparison of the microbiota and antibiotic susceptibility pattern in CF bronchiectasis versus non-CF bronchiectasis would help to improve the management of both conditions. METHODS: Two authors will independently search the electronic databases PubMed, EMBASE, the Cochrane Library, and LIVIVO, for studies reporting bacterial colonization of the respiratory tract in adults and children diagnosed with bronchiectasis in either CF or non-CF. We will include studies examining any respiratory tract specimen, using conventional bacterial culture or other specialized techniques such as molecular methods. We will also examine the antimicrobial susceptibility patterns in people with CF bronchiectasis versus non-CF bronchiectasis. The authors will independently assess the risk of bias in each included study using the Newcastle Ottawa Scale (NOS). We will present the data with descriptive statistics and provide pooled estimates of outcomes, wherever it is feasible to perform meta-analysis. Heterogeneity in studies will be explored by visual inspection of forest plots as well as using the Higgins and Thompson I2 method. We will contact the corresponding authors of studies where data is/are missing and try to obtain the missing data. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on pre-set criteria. We will prepare a summary of findings' table and assess the confidence in the evidence using the GRADE methodology. DISCUSSION: To date, there are no locally applicable evidence-based guidelines for antimicrobial treatment of non-CF bronchiectasis patients. In general, treatment is based on extrapolation of evidence in people with CF bronchiectasis. An insight into the microbiota and antimicrobial susceptibility patterns in the two conditions would facilitate appropriate rather than empiric antimicrobial therapy and hopefully reduce the burden of antimicrobial resistance created by rampant usage of antibiotics. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered in PROSPERO on July 26, 2020 (PROSPERO registration number: CRD42020193859 ).

Primary Immunodeficiency in a 74-Year-Old Male With Chronic Productive Cough: A Rare Case of Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency. It presents with variable degrees of immunodeficiency resulting in a variety of clinical presentations and complications. This report describes the case of newly diagnosed CVID in a 74-year-old man with no history of recurrent infections or hospitalizations. He presented with chronic productive cough, wheezing, shortness of breath and fatigue. Physical examination showed bilateral rhonchi and scattered wheezes. Pulmonary function tests showed moderate obstructive defect with partial reversibility and decreased diffusion lung capacity for carbon monoxide (DLCO). Chest computed tomography (CT) showed bilateral lower lobe peribronchial thickening and mildly enlarged lymph nodes in the mediastinum and upper abdomen. Bronchoscopy with alveolar lavage was done and respiratory samples grew Moraxella. He had negative acid fast bacillus stain and negative tuberculosis and fungal cultures. He received a course of antibiotics resulting in brief improvement in symptoms followed by another exacerbation. Repeat sputum cultures grew Pseudomonas. Further testing showed severely depressed levels of immunoglobulin. His symptoms ultimately improved with immunoglobulin replacement therapy. A broad differential, including CVID, needs to be considered in working up a patient with a chronic productive cough and recurrent lower respiratory tract infection.

Airway microbiota is associated with the severity of non-CF bronchiectasis.

BACKGROUND: Airway microbiota are associated with several chronic respiratory diseases. However, limited studies examined microbiota in non-cystic fibrosis (non-CF) bronchiectasis, especially its relationship with severity and immunology. OBJECTIVES: We characterized the microbiota of patients with different severities of bronchiectasis and examined the correlation between microbiota and the immunological indices. MATERIALS AND METHODS: The microbiota of 63 sputum samples from 40 patients with bronchiectasis were analyzed by 16S rRNA gene sequencing. Blood tests and related immunological indices were detected. RESULTS: According to the baseline data of patients with bronchiectasis, we found that more severe bronchiectasis was accompanied by lower prealbumin levels. The 16S rRNA sequencing analyses demonstrated that Pseudomonas-dominated microbiota produced lower levels of interleukin-4 (IL-4) and transforming growth factor-ß (TGF-ß) compared to other-dominated microbiota. The airway microbiota of patients with mild bronchiectasis clustered apart from those of patients with severe bronchiectasis, which correlated with IL-4 and other clinical indices. CONCLUSION: There are differences in the airway microbiota between patients with mild and severe bronchiectasis. The airway microbiota was related to some clinical indices that represent effects on the immune system.

Effectiveness of hypertonic saline nebulization in airway clearance in children with non-cystic fibrosis bronchiectasis: A randomized control trial.

INTRODUCTION: Failure to expectorate mucus resulting in progressive airway damage is the hallmark of bronchiectasis. Therefore effective airway clearance techniques (ACT) is the key step in its management. The aim of this study was to evaluate the efficacy of 3% hypertonic saline (HS) pre-medication in ACT in children with non cystic fibrosis (non-CF) bronchiectasis. METHODS: In this randomized crossover control trial five to 15 year old children, diagnosed with non-CF bronchiectasis were randomized either to receive 200 µg of inhaled salbutamol followed by HS nebulization (test) or only 200 µg of inhaled salbutamol, before chest physiotherapy which is the conventional ACT (controls) for 8 weeks. Inhaled salbutamol was administered via a pressurized metered dosed inhaler with a valved holding chamber. After completion of first phase both groups went through one month washout period, before being crossed over to the opposite arms in the second phase. Spirometric parameters and number of exacerbations were recorded at the end of phase I, washout period and phase II. RESULTS: Fifty two out of 63 enrolled completed the study. Baseline characteristics of the two groups were similar. A significantly higher mean improvement was seen in predicted forced expiratory volume in 1 s in the HS arm during phase 1 (HS = 14.15 ± 5.50 vs. conventional = 5.04 ± 5.55, p = .001) and phase II (HS = 10.81 ± 5.51 vs. conventional = 3.54 ± 5.13, p = .001) compared to conventional ACT arm. HS group showed a significantly higher mean improvement in predicted forced vital capacity in phase I (HS = 13.77 ± 5.73 vs. conventional = 7.54 ± 4.90, p = .001) and phase II, (HS = 9.42 ± 7.00 vs. conventional = 4.42 ± 4.00, p = .003). Mean number of exacerbations experienced by a single child during phase I (2 months) were significantly less (p = .001) in HS arm (0.42 ± 0.64) compared to that of conventional arm (1.30 ± 1.05) butthis difference was not significant in phase II (HS = 0.65 ± 0.74 and conventional = 1.03 ± 0.77, p = .074). CONCLUSION: Incorporating HS nebulization into ACT is an effective strategy to improve dynamic lung volumes and morbidity in children with non-CF bronchiectasis.

Asthma-Like Features and Anti-Asthmatic Drug Prescription in Children with Non-CF Bronchiectasis.

Bronchiectasis and asthma may share some characteristics and some patients may have both conditions. The present study aimed to examine the rationale of prophylactic inhaled corticosteroids (ICS) prescription in children with bronchiectasis. Data of children with radiologically established bronchiectasis were retrospectively reviewed. Episodes of dyspnea and wheezing, spirometric indices, total serum IgE, blood eosinophil counts, sensitization to aeroallergens, and air-trapping on expiratory CT scans, were recorded. The study included 65 children 1.5-16 years old, with non-CF bronchiectasis. Episodes of dyspnea or wheezing were reported by 22 (33.8%) and 23 (35.4%), respectively. Skin prick tests to aeroallergens (SPTs) were positive in 15 (23.0%) patients. Mosaic pattern on CT scans was observed in 37 (56.9%) patients. Dyspnea, presence of mosaic pattern, positive reversibility test, and positive SPTs were significantly correlated with the prescription of ICS. The prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like characteristics. The difficulty to set the diagnosis of real asthma in cases of bronchiectasis may justify the decision of clinicians to start an empirical trial with ICS in certain cases.

Etiology, Clinical, Radiological, and Microbiological Profile of Patients with Non-cystic Fibrosis Bronchiectasis at a Tertiary Care Hospital of Pakistan.

Objectives To identify the etiology of non-cystic fibrosis bronchiectasis (NCFB), to assess the clinical presentation, radiological findings, and microbiological profile of patients presenting with a diagnosis of bronchiectasis in a tertiary care center of Pakistan. Methods This was a prospective observational cohort study where patients with a diagnosis of bronchiectasis proven by high-resolution computed tomography (HRCT) were evaluated for etiology, clinical characteristics, microbiology, radiology, spirometric profile, and in-hospital outcomes. Results During the study period, 196 patients were diagnosed with NCFB. The majority of the patients were men 76.5% (n = 150) and 83.6% (n = 163) of the total patients were younger than 60 years of age. The majority of these patients (58.7%, n = 111) had a duration of symptoms between 5-10 years. The etiology of bronchiectasis was identified in 92.9% of cases. Post-infectious bronchiectasis was the most common cause (67.8%, n = 133), followed by chronic obstructive pulmonary disease (COPD) (9.2%, n = 18), and allergic bronchopulmonary aspergillosis (ABPA) (7.1%, n = 14). Among the post infectious causes, a history of TB was present in 85% (n = 114/133) of patients. Obstructive impairment was the most common spirometric pattern, observed in 68.9% (n = 135) of patients. Pseudomonas aeruginosa was the most commonly isolated organism (36.2%, n = 71). Hemoptysis was the most frequent complication found in 20.9% of patients (n = 41). Out of these 196 patients, 94.4% (n = 185) received medical management and were discharged from the hospital. Respiratory failure was significantly associated with the Pseudomonas group as compared to non-pseudomonas group [(n = 21 (29%) vs n = 18 (14.4%) p = 0.01]. During hospitalization seven patients (3.6%) were died because of respiratory failure. Conclusions Post TB bronchiectasis was the leading cause of non-cystic fibrosis (CF) bronchiectasis in this cohort, with Pseudomonas was the commonest pathogen isolated from the respiratory specimen, which was significantly associated with respiratory failure. On spirometry, obstructive impairment was found in the majority of patients and hemoptysis was the most frequent complication.