Non-cystic Fibrosis Bronchiectasis Patients Research Articles

The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species.

Brensocatib is a novel, oral, selective, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), which activates several neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) in the bone marrow during the early stage of neutrophil maturation. These NSPs are associated with pathogen destruction and inflammatory mediation; their dysregulated activation can result in excess secretion of active NSPs causing damaging inflammation and contributing to neutrophil-mediated inflammatory and autoimmune diseases. Pharmacological inhibition of DPP1 in the bone marrow could therefore represent an attractive strategy for these neutrophil-driven diseases. A completed Phase 2 trial in non-cystic fibrosis bronchiectasis patients (ClinicalTrials.gov number NCT03218917; EudraCT number: 2017-002533-32) indeed demonstrated that administration of brensocatib attenuated the damaging effects of chronic inflammation by inhibiting the downstream activation of NSPs. To support a range of preclinical programs and further understand how rodent species and strains may affect brensocatib's pharmacokinetic (PK) profile and its pharmacodynamic (PD) effects on NE, PR3, and CatG, an extensive naïve dosing study with brensocatib at different dosing levels, frequencies, and durations was undertaken. Dose-dependent PK exposure responses (AUC and Cmax) were observed regardless of the rodent species and strain. Overall, mice showed greater reduction in NSP activities compared to rats. Both mice and rats dosed once daily (QD) had equivalent NSP activity reduction compared to BID (twice a day) dosing when the QD dose was 1.5-times the BID daily dose. For both mouse strains, CatG activity was reduced the most, followed by NE, then PR3; whereas, for both rat strains, PR3 activity was reduced the most, followed by CatG, and then NE. Maximum reduction in NSP activities was observed after ∼7 days and recoveries were nearly symmetrical. These results may facilitate future in vivo brensocatib study dosing considerations, such as the timing of prophylactic or therapeutic administration, choice of species, dosage and dosing frequency.

Microbiology sampling in non-cystic fibrosis bronchiectasis cases from northern Alberta.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease resulting in chronic cough, thick sputum, and lower airway microbial colonization, akin to patients with cystic fibrosis (CF). NCFB is a common, yet under recognized entity which inflicts significant morbidity and mortality particularly to older individuals, with a rising prevalence in the developed world. Given that sputum cultures are a non-invasive method to characterize the lower airway microbiota in NCFB patients, for which pathogenic organisms are associated with worsened outcomes, we sought to characterize the microbiological pattern and clinical outcomes associated with sputum culture in a cohort of NCFB patients from Western Canada. A total of 20 subjects were prospectively recruited from various bronchiectasis clinics across the Greater Edmonton area. A retrospective chart review and a symptoms questionnaire was performed, gathering information not limited to symptoms, comorbidities, exacerbations, hospitalizations, sputum production, and sputum culture results over the prior 5 years. Subjects reported frequent hospitalization alongside a significant burden of symptoms. A large majority of sputum cultures grew pathogenic organisms such as Haemophilus influenzae and Pseudomonas aeruginosa. We also note the considerable waste and inefficiency associated with sputum cultures, outlining areas for which this important diagnostic modality can be improved. Accurate characterization of the airway microbiota alongside efficient delivery of health services are key to ensuring the proper treatment of individuals with NCFB, given their high disease burden and frequent hospitalization.

The relation between inspiratory muscle strength and bacterial colonization and other clinical factors in patients with non-cystic fibrosis bronchiectasis.

This study aimed to investigate whether inspiratory muscle strength was associated with bacterial colonization and other clinical outcomes and whether bacterial colonization was associated with clinical outcomes in patients with non-cystic fibrosis bronchiectasis (NCFB). Eighty-six patients were enrolled in a cross-sectional study. Patients were divided into two groups according to the presence of inspiratory muscle weakness and bacterial colonization. Parameters were compared between groups. Bronchiectasis etiologies were post-infectious, Kartagener's syndrome, and primary ciliary dyskinesia. The median value of MIP was -68, and MEP was 89 cm H2O in all patients. Although the ratio of bacterial colonization was similar to patients without inspiratory muscle weakness, the inspiratory muscle weakness group had a higher number of females, lower FEV1, FVC, ISWT, CRQ, higher MRC, E-FACED, SGRQ, number of hospitalization (p<0.05). When colonized and non-colonized patients were compared, MIP, and MEP were similar in spite of adjusted BMI, age, and sex. FEV1, FVC, ISWT, and ESWT were lower, and E-FACED scores (p<0.05) were higher in colonized patients. Although inspiratory muscle strength was not associated with bacterial colonization in NCFB patients, it is an important factor that could be linked to disease severity, pulmonary functions, quality of life, and exercise capacity. Bacterial colonization was also associated with severe disease, deteriorated pulmonary functions, and exercise capacity.

EE476 The Cost of Non-Cystic Fibrosis Bronchiectasis (NCFB) Patients with Commercial Insurance or Medicare Coverage in the United States

Non-Cystic Fibrosis Bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterized by irreversibly dilated airways and recurrent pulmonary infections. Concomitant infection with Pseudomonas aeruginosa is associated with greater lung function impairment, more frequent exacerbations, greater hospitalization risk, and mortality. NCFB exacerbations are defined as an increase in daily symptoms including cough, sputum, malaise, fatigue, and difficulty breathing. The cost of NCFB illness with Pseudomonas aeruginosa and frequent acute exacerbations have not been quantified.

COVID-19 PANDEMİSİ SIRASINDA KİSTİK FİBROZİS DIŞI BRONŞEKTAZİ HASTALARINDA COVID-19 FOBİSİ VE FİZİKSEL AKTİVİTE DÜZEYİ

Purpose: The COVID-19 pandemic period may affect physical and mental health of non-cystic fibrosis (CF) bronchiectasis patients. The aim of this study was to compare COVID-19 phobia, quality of life, health anxiety, physical activity level and sleep quality during the pandemic between patients with non-CF bronchiectasis and healthy controls.&#x0D; Methods: Thirty non-CF bronchiectasis patients and 44 healthy controls were included. COVID-19 phobia (Coronavirus 19 Phobia Scale (CP19-S)), quality of life (Nottingham Health Profile (NHP)), health anxiety (Health Anxiety Inventory (HAI)), physical activity level (short form of the International Physical Activity Questionnaire (IPAQ-SF)) and sleep quality (Pittsburgh Sleep Quality Index (PSQI)) were evaluated.&#x0D; Results: NHP energy, pain, and physical mobility scores and moderate-intensity physical activity levels were significantly lower; PSQI sleep disturbance score was significantly higher in patients compared with controls (p0.05). The majority of patients and controls did not meet the recommended levels of moderate or high-intensity physical activity per week.&#x0D; Conclusion: The COVID-19 pandemic has resulted in a decline in quality of life, reduced moderateintensity physical activity, and increased sleep disturbances among non-CF bronchiectasis patients. Both patients and healthy individuals have experienced coronaphobia and exhibited low levels of physical activity. These results reveal the importance of providing physical activity counseling during the pandemic period.

Down-expression of Foxj1 on airway epithelium with impaired cilia architecture in non-cystic fibrosis bronchiectasis implies disease severity.

The pathogenesis of non-cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non-cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. Lung tissue sections excised from 47 patients with non-cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. Of the 47 patients with non-cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non-cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non-cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89)μm versus (7.34 ± 0.71)μm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non-cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. Foxj1 declined in the airway epithelium of patients with non-cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity.

Risk factors and prognostic value of osteoporosis in hospitalized patients with bronchiectasis

BackgroundThe risk factors for osteoporosis and its prognostic value in patients with bronchiectasis is not well characterized. We explored the risk factors for osteoporosis and its prognostic impact in hospitalized non-cystic fibrosis bronchiectasis (NCFB) patients in Southeast China.MethodsThis observational cohort study consecutively enrolled 179 hospitalized patients with NCFB bronchiectasis between 2017 and 2021. The risk factors and the impact of osteoporosis on all-cause mortality were assessed.Results21.2% (38/179) of hospitalized NCFB patients were diagnosed with osteoporosis. Patients with osteoporosis had more severe symptoms (assessed by chronic airway assessment test, CAT, median 22 vs. 17, P = 0.017), poorer quality of life (assessed by St. George Respiratory Questionnaires, SQRC, median 42 vs. 27, P = 0.007), more severe disease stage (assessed by bronchiectasis severity index, BSI, median 14 vs. 11, P = 0.02), more comorbidities (assessed by Bronchiectasis Aetiology Comorbidity Index, BACI, median 5 vs. 4, P = 0.021) than patients without. Age, female sex, anemia, post-infection, and history of regular inhaled corticosteroid treatment were independent risk factors for osteoporosis in those patients. 21 patients (11.7%) died over a median follow-up period of 32 months. The all-cause mortality in NCFB patients with osteoporosis [28.94% (11/38)] was significantly higher than those without osteoporosis [7.09% (10/141)] [hazard ratio (HR) 5.34, 95% confidence interval (CI) 2.26–12.67, P < 0.001]. After adjusting for BSI and other confounding factors, osteoporosis was still independently associated with all-cause mortality in hospitalized NCFB patients (HR 4.29, 95% CI 1.75–10.49, P < 0.001).ConclusionsOsteoporosis had an independent effect on all-cause mortality in hospitalized NCFB patients. Management of comorbidities, including bone health, is a critical aspect of treating NCFB patients.

The Impact of Cystic Fibrosis- and Noncystic Fibrosis-Bronchiectasis on Pulmonary Artery Wall Thickness and Right Heart Functions Assessed by Speckle-Tracking Echocardiography.

Right heart functions are affected in patients with bronchiectasis as a result of pulmonary hypertension induced by chronic hypoxemia. Pulmonary artery wall thickness has recently been introduced as a sign of intensive and prolonged inflammation. The aim of this study was to analyze right ventricular and right atrial functions and to mea-sure pulmonary artery wall thickness in patients with cystic fibrosis-bronch iecta sis in comparison to those with noncystic fibrosis-bronchiectasis and healthy individuals. We studied 36 patients with cystic fibrosis-bronchiectasis, 34 patients with noncystic fibrosis-bronchiectasis, and 32 age- and sex-matched control subjects. Lung function tests were performed. All subjects underwent comprehensive echocardiographic evaluation including conventional, tissue Doppler, speckle-tracking, and pulmonary artery wall thickness measurements. Right ventricular global longitudinal strain and global longitudinal right atrial strain during ventricular systole decreased in cystic fibrosis-bronchiectasis group compared with noncystic fibrosis-bronchiectasis and control groups (P <.001, both). Conversely, pulmonary artery wall thickness was increased in cystic fibrosis-bronchiectasis group in comparison to other groups (P <.001). Moreover, right ventricular global longitudinal strain was lower and pulmonary artery wall thickness was higher in patients with airflow obstruction (P <.001 and P =.025, respectively) than in those without. Only right ventricular global longitudinal strain was significantly correlated with pulmonary function test parameters. The negative effect of cystic fibrosis on right ventricular and right atrial functions was independent of age, gender, and disease duration. Our study showed that right ventricular and right atrial functions were deteriorated and pulmonary artery wall was thickened in cystic fibrosis-bronchiectasis patients more than noncystic fibrosis-bronchiectasis patients. Right ventricular global longitudinal strain detected subclinical right ventricular dysfunction and was associated with the severity of pulmonary disease.

Simultaneous evaluation of the fractional exhaled nitric oxide and blood eosinophil count of T2-high endotype in patients with non-cystic fibrosis bronchiectasis.

Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25ppb; BEC ≥200/µL). Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.

EE187 Healthcare Resource Utilization in Non-Cystic Fibrosis Bronchiectasis (NCFB) Patients With Commercial Insurance Coverage in the US

EE187 Healthcare Resource Utilization in Non-Cystic Fibrosis Bronchiectasis (NCFB) Patients With Commercial Insurance Coverage in the US

Profile of patients with post-tuberculosis bronchiectasis in a tertiary care hospital in Brazil

Bronchiectasis are abnormal permanently dilated bronchi which lead to chronic cough and other respiratory symptoms. Though tuberculosis (TB) is a common cause of bronchiectasis, data on this association are scarce. The objective of this study was to describe the profile of patients with post-TB bronchiectasis at a tertiary hospital in the southern region of Brazil. This was a retrospective study with data from patients in follow-up at our hospital from January 2005 to December 2020. We included patients 14 years of age or older who had bronchiectasis on chest computed tomography and a history of pulmonary TB. We excluded patients with bronchiectasis due to other causes or with confirmed non-tuberculous mycobacteria infection. We included 54 of the 204 non-cystic fibrosis bronchiectasis patients seen at our hospital during the study period. Most of the patients were female, older, and non-smokers. Less than a third had chronic bronchial infection by some agent. More than two thirds had some type of ventilatory defect, the most common being obstruction. More than half had upper-lobe impairment. Severity of the disease seemed to be equally distributed from mild to severe. Treatment was varied, including bronchodilators, inhaled corticosteroids, and azithromycin. We found that the profile of patients in our hospital is similar to that described in other studies, with slight differences in regard to microbiology and treatment.

Multidrug-resistant Pseudomonas aeruginosa is predisposed to lasR mutation through up-regulated activity of efflux pumps in non-cystic fibrosis bronchiectasis patients.

BackgroundMultidrug-resistant (MDR) Pseudomonas aeruginosa is a frequent opportunistic pathogen that causes significant mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Although the quorum sensing (QS) system is a potential target for treatment, lasR mutants that present with a QS-deficient phenotype have been frequently reported among clinical P. aeruginosa isolates. We aimed to investigate whether antibiotic resistance would select for lasR mutants during chronic P. aeruginosa lung infection and determine the mechanism underlying the phenomenon.MethodsWe prospectively evaluated episodes of chronic P. aeruginosa lung infections in NCFB patients over a 2-year period at two centers of our institution. QS phenotypic assessments and whole-genome sequencing (WGS) of P. aeruginosa isolates were performed. Evolution experiments were conducted to confirm the emergence of lasR mutants in clinical MDR P. aeruginosa cultures.ResultsWe analyzed episodes of P. aeruginosa infection among 97 NCFB patients and found only prior carbapenem exposure independently predictive of the isolation of MDR P. aeruginosa strains. Compared with non-MDR isolates, MDR isolates presented significantly QS-deficient phenotypes, which could not be complemented by the exogenous addition of 3OC12-HSL. The paired isolates showed that their QS-phenotype deficiency occurred after MDR was developed. Whole-genome sequencing analysis revealed that lasR nonsynonymous mutations were significantly more frequent in MDR isolates, and positive correlations of mutation frequencies were observed between genes of lasR and negative-efflux-pump regulators (nalC and mexZ). The addition of the efflux pump inhibitor PAβN could not only promote QS phenotypes of these MDR isolates but also delay the early emergence of lasR mutants in evolution experiments.ConclusionsOur data indicated that MDR P. aeruginosa was predisposed to lasR mutation through the upregulated activity of efflux pumps. These findings suggest that anti-QS therapy combined with efflux pump inhibitors might be a potential strategy for NCFB patients in the challenge of MDR P. aeruginosa infections.

Correlation among clinical, functional and morphological indexes of the respiratory system in non-cystic fibrosis bronchiectasis patients.

BackgroundNon-cystic fibrosis bronchiectasis (NCFB) is a heterogeneous disease, which assessment and severity can’t be defined by one particular instrument but using a multidimensional score. Thus, in additional to traditional methods, alternative tools have been developed to assist these patients’ evaluation.ObjectiveTo correlate functional and morphological indexes with severity and dyspnea in NCFB patients, focusing on the correlation between the impulse oscillometry system (IOS) and the quantitative analysis of computed tomography (CT).MethodsClinically stable NCFB patients, between 18 and 80 years old were submitted to clinical, functional and morphological evaluations assessed by Bronchiectasis Severity Index (BSI) and Medical Research Council (MRC) scale; spirometry and IOS; and subjective and quantitative Chest CT scans analysis, respectively.ResultsThis study included 38 patients. The best correlations obtained between functional and morphological airway indexes were: resistance at 5 Hz—R5 and the normalized thickness of bronchial walls—Pi10 (r = 0.57), and the mean forced expiratory flow (FEF25-75%) and CT score (r = -0.39). BSI as well as MRC showed higher correlations with the quantitative automated analysis of CT (BSI and Pi10: r = 0.41; MRC and Pi10: r = 0.35) than with subjective CT score (BSI and CT score: r = 0.41; MRC and CT score: r = 0.15); and moderate and weak correlations were obtained on both functional airway indexes (BSI and peripheral airways resistance - R5-R20: r = 0.53; BSI and forced expiratory volume at the first second—FEV1: R = -0,64; MRC and R5-R20: r = 0.42; and MRC and VEF1: r = -0.45).ConclusionIn NCFB patients, compartmentalized methods for assessing the respiratory system (IOS and the automated quantitative CT analysis) have a good correlation with severity and dyspnea.

In bronchiectasis, poor physical capacity correlates with poor quality of life

ABSTRACT Purpose Patients with bronchiectasis (BE) who suffer frequent exacerbations are likely to experience negative effects on quality of life (QoL) and require more healthcare utilization. We aimed to discover, in a cohort of Finnish BE patients, those risk factors that influence QoL. Methods Non-cystic fibrosis BE patients of a Helsinki University Hospital cohort were examined with high-resolution computed tomography (HRCT) of the chest. They completed a disease-specific quality of life-bronchiectasis (QoL-B) questionnaire in Finnish translation. We considered scores in the lowest quarter (25%) of that QoL-B scale to indicate poor QoL. The bronchiectasis severity index (BSI), FACED score, and modified Medical Research Council (mMRC) dyspnoea scale were used. Results Overall, of 95 adult BE patients, mean age was 69 (SD ± 13) and 79% were women. From the cohort, 82% presented with chronic sputum production and exacerbations, at a median rate of 1.7 (SD ± 1.6). The number of exacerbations (OR 1.7), frequent exacerbations (≥3 per year) (OR 4.9), high BSI score (OR 1.3), and extensive disease (≥3 lobes) (OR 3.7) were all predictive of poor QoL. Frequent exacerbations were associated with bronchial bacterial colonisation, low forced expiratory volume in 1 s (FEV1), and radiological disease severity. Based on the BSI, 34.1% of our cohort had severe disease, with 11.6% classified as severe according to their FACED score. The mMRC dyspnoea score (r = −0.57) and BSI (r = −0.60) correlated, in the QoL-B questionnaire, negatively with physical domain. Conclusion The strongest determinants of poor QoL in the cohort of Finnish BE patients were frequent exacerbations, radiological disease severity, and high BSI score. Neither comorbidities nor BE aetiology appeared to affect QoL. Reduced physical capacity correlated with dyspnoea and severe disease. Study registration University of Helsinki, Faculty of Medicine, 148/16.08.2017.

Ciliary and immune dysfunctions and their genetic background in patients with non-cystic fibrosis bronchiectasis in Central Iran.

Bronchiectasis is usually caused by recurrent bacterial infections and is characterized by irreversible dilation of the bronchi. In this study, we aimed to give an overview of the genetic backgrounds of patients with non-cystic fibrosis bronchiectasis (NCFB) that have been suspected to an underlying ciliary dysfunction or inborn error of immunity (IEI). This is a retrospective cross-sectional study. Seventy-one NCFB patients who were referred to the Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran, from 1996 to 2020 were included. These patients were referred to this center for immunological and genetic evaluation. Genetic analysis with whole-exome sequencing and Sanger sequencing was confirmed in 30 patients. However, the genetic evaluations of 41 patients were either still under evaluation or the patients had refused to be genetically evaluated. Thirty-eight of our 71 patients (53.52%) were diagnosed with ciliary dysfunction and the detected mutations included mutations in the CCDC65, DNAH11, RSPH1, CCDC40, and GAS8 genes as well as a novel mutation. Thirty-three patients (46.47%) had an IEI and the detected mutations included mutations of the following genes: TNFRSF13B, PTPN2, ZNF341 BTK, TCF3, CD79a, PIK3CD, JAGN1, WAS, RFXANK, STK4, GSDMD, and NEMO. This study presents an overview of the underlying ciliary and immune dysfunctions and their genetic mutations in NCFB in a highly consanguine population. This would give us a better understanding of the etiologies and the known and novel genetic mutations in NCFB in Iran and, in turn, in the Middle East and North Africa (MENA) region.

Risk Factors Associated with Impairment in Pulmonary Diffusing Capacity among Patients with Noncystic Fibrosis Bronchiectasis.

This study aims to investigate the risk factors associated with impaired pulmonary diffusing capacity among patients with noncystic fibrosis bronchiectasis (NCFB) and compare the predictive value of several scoring systems for the impairment in these patients. Between July 2019 and June 2021, patients who were admitted to the hospital and diagnosed with NCFB were included in this study. Clinical data were collected and analyzed retrospectively. A total of 175 NCFB patients were included in the analysis. Multivariate logistic regression analysis revealed that impaired pulmonary diffusing capacity diagnosed by carbon monoxide diffusing capacity (DLCO) <80% prediction was associated with age, Reiff score, body mass index (BMI), comorbid chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Disease duration, frequency of exacerbation, hemoglobin level, and COPD were independent risk factors for impaired pulmonary diffusing capacity diagnosed by DLCO/alveolar volume (VA) <80% prediction. Age, Reiff score, and smoking status were independent risk factors for decreased VA diagnosed by VA <80% prediction. The areas under the curve (AUC) for discrimination of DLCO <80% prediction were 0.822 (0.760–0.885) for Bronchiectasis Severity Index (BSI), 0.787 (0.718–0.856) for FACED, 0.795 (0.729–0.863) for E-FACED, and 0.767 (0.694–0.839) for modified Medical Research Council (mMRC) scores; the AUC for discrimination of DLCO/VA <80% prediction was 0.803 (0.727–0.880) for BSI, 0.752 (0.669–0.835) for FACED, 0.757 (0.676–0.839) for E-FACED, and 0.762 (0.679–0.845) for mMRC, respectively. The BSI had the largest AUC, but the differences between those scoring systems had no statistical significance (P=0.181 for DLCO <80% prediction and P=0.105 for DLCO/VA <80% prediction). The mMRC score (up to 2 grades) showed a high specificity for discriminating diffusing dysfunction (88.3% for DLCO <80% prediction and 76.1% for DLCO/VA <80% prediction). In NCFB patients, several factors such as age, Reiff score, BMI, exacerbation frequency, disease duration, and comorbid COPD and ILD were associated with impaired pulmonary diffusing capacity, which requires more attention in managing those patients. In addition, several scoring methods, including a simple index of mMRC, showed a comparable and moderate performance for predicting pulmonary diffusing impairment and would facilitate the systematic evaluation of the diffusing capacity of NCFB patients.

Respiratory and Peripheral Muscle Weakness and Body Composition Abnormalities in Non-Cystic Fibrosis Bronchiectasis Patients: Gender Differences.

As demonstrated in COPD, bronchiectasis patients may experience respiratory and peripheral muscle dysfunction. We hypothesized that respiratory and peripheral (upper and lower limbs) muscle function and nutritional status may be more significantly altered in female than in males for identical age and disease severity. In mild-to-moderate bronchiectasis patients (n = 150, 114 females) and 37 controls (n = 37, 21 females), radiological extension, maximal inspiratory and expiratory pressures (MIP and MEP), sniff nasal inspiratory pressure (SNIP), hand grip and quadriceps muscle strengths, body composition, and blood analytical biomarkers were explored. Compared to the controls, in all bronchiectasis patients (males and females), BMI, fat-free mass index (FFMI), fat tissue, upper and lower limb muscle strength, and respiratory muscle strength significantly declined, and FFMI, fat tissue, and quadriceps muscle function were significantly lower in female than male patients. In patients with mild-to-moderate bronchiectasis, respiratory and peripheral muscle function is significantly impaired and only partly related to lung disease status. Quadriceps muscle strength was particularly weakened in the female patients and was negatively associated with their exercise tolerance. Muscle weakness should be therapeutically targeted in bronchiectasis patients. Body composition and peripheral muscle function determination should be part of the comprehensive clinical assessment of these patients.

A retrospective correlative profiling of lung functions, microbiological, radiological, periodontal, hematological parameters in noncystic fibrosis bronchiectasis patients of North India

Introduction:Noncystic fibrosis bronchiectasis (NCFB) is a neglected debilitating condition with scarce epidemiological literature explaining its geographical heterogeneity, especially in lower and middle-income countries. This study aimed to assess and correlate the functional profile of NCFB patients and evaluate the correlation of body mass index (BMI) with several disease variables.Methods:This mixed-method retrospective research study was conducted on 124 radiologically confirmed NCFB patients in terms of various qualitative and quantitative variables.Results:Restrictive ventilatory defect was the most common type with the preponderance of male former smokers. Mean platelet lymphocyte ratio (PLR; 104.08 ± 73.59) revealed certain degree of systemic inflammatory burden with a slightly higher mean peripheral leukocyte count (10665.19 ± 4268.81 cell/mm3) and eosinophilia of >2%. Almost all patients had periodontal disease with a higher prevalence of chronic periodontitis (54.83%). Moderately severe and predominantly cystic radiological type was encountered with 61.2% patients positive for Pseudomonas aeruginosa. Bronchiectasis aetiology comorbidity index (BACI) i.e., 2.34 ± 2.37 represented an intermediate mortality risk in our patients. On basis of BMI, majority were young underweights with poor pulmonary functions while PLR skewed toward overweight patients (nonsignificant P > 0.05). Forced expiratory volume/forced vital capacity displayed a negative weak moderately significant correlation with BACI (r = −0.24; P = 0.008). Peripheral lymphocyte count demonstrated a weak negative but significant correlation with modified Reiff score (r = −0.20; P = 0.023) while serum neutrophil count had a weak negative moderately significant correlation with hemoglobin (r = −0.20; P = 0.023).Conclusions:NCFB bears great heterogeneity with distinct geographical phenotypes and should be correlated thoroughly in terms of peripheral leukocytes count, pulmonary functions, radiology, BMI, and coexisting comorbidities for adequate management.

Outcomes and survival following lung transplantation in non-cystic fibrosis bronchiectasis.

Disease-specific outcomes in patients with non-cystic fibrosis bronchiectasis following lung transplantation are not well described.We performed a retrospective analysis to describe outcomes in these patients. Patients with non-cystic fibrosis bronchiectasis who have undergone lung transplantation in the USA were identified using the Organ Procurement and Transplant Network database. Survival data were analysed for the post-lung allocation score period with Kaplan–Meier curves, and a log-rank test was conducted to compare survival data among an age-, sex- and activation date-matched non-cystic fibrosis bronchiectasis cohort.721 patients with non-cystic fibrosis bronchiectasis were listed for lung transplantation between March 1992 and September 2019. 407 patients received lung transplantation with a median age at listing of 47 years. The Kaplan–Meier survival analysis for lung transplantation recipient non-cystic fibrosis bronchiectasis patients during the post-lung allocation score period at 1, 5 and 10 years was 87%, 53% and 16%, respectively. The median survival time post-lung transplantation is 6.0 years (interquartile range: 2.3–11.9 years), which is similar to an age- and sex-matched cohort (p=0.86).This retrospective analysis demonstrates that median survival after lung transplantation in non-cystic fibrosis bronchiectasis was similar to other lung transplantation recipients over the study period. We suggest that the development of specific criteria for lung transplantation in non-cystic fibrosis bronchiectasis may improve patient selection and benefit a larger group of patients with this therapy.

Sputum Neutrophil Elastase in pediatric cystic fibrosis and non-cystic fibrosis bronchiectasis

Abstract Objective To assess the value of sputum neutrophil elastase as a biomarker of severity in cases of non-cystic fibrosis bronchectasis &amp; cystic fibrosis. Methods This cross-sectional study was conducted on 50 bronchiectasis patients aged from 1 to 13 years presented to pediatric chest clinic and department of Ain shams university hospital., there were classified into 2 groups; Group A cystic fibrosis patients(30) and group B non-cystic fibrosis bronchiectasis patients(20). Inclusion criteria :children aged from 1 to 16 years, patients were diagnosed with bronchiectasis clinically and with HRCT chest and cystic Fibrosis patients were diagnosed by positive sweat chloride test and genetic study. Exclusion Criteria includes no other known chronic lung diseases. All patients were evaluated by full medical history and full clinical examination, the following lab investigations were done :sweat chloride test, CFTR mutation study, sputum sampling and culture. Quantitative sputum neutrophil elastase assay was done, and the severity of disease was assessed using clinical scores as SK score ,FACED score and bronchiectasis severity index and by using radiological scores as Bhalla and modified Reiff score. Results Steatorrhea was more prevalent among cystic fibrosis patients (80%) than non-CF bronchiectasis patients (0%).(P = 0.00). Clubbing was more prevalent among non -cystic fibrosis bronchectasis (10) (50 %), than cystic fibrosis (2 patients) (6.7 %).(P = 0.00). In cystic fibrosis, neutrophil elastase was significantly higher among severe group (126 ng/mL) than among the moderate (30 ng/mL) and mild (16 ng/mL) groups.(P = 0.00). While in non-CF bronchiectasis patients, neutrophil elastase was significantly higher among severe group (67 ng/mL) than among the moderate (24 ng/mL) and mild (11 ng/mL) groups.(P = 0.00) Conclusion There was a significant correlation between sputum neutrophil elastase and disease severity in bronchiectasis (both cystic fibrosis and non-CF).