Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co-existent bronchiectasis.

PublishedArticleCopyright © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty LtdAim: Patients with rheumatoid arthritis (RA) and co-existent Bronchiectasis (BRRA) have a 5-fold increased mortality compared to rheumatoid arthritis alone. Yet previous studies have found no difference in clinical and serological markers of RA disease severity between BRRA patients and RA alone. RA disease activity measures such as DAS28-CRP and anti-cyclic citrullinated peptide antibodies (anti-CCP) however have not been studied, so we assessed these parameters in patients with BRRA and RA alone. Methods: BRRA patients (n = 53) had HRCT proven bronchiectasis without any interstitial lung disease and ≥2 respiratory infections/year. RA alone patients (n = 50) had no clinical or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor (IgM) and anti-CCP were measured in all patients, together with detailed clinical and radiology records. Results: In BRRA, BR predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs. 2.59), higher levels of anti-CCP (89 vs. 46%) and RF (79 vs. 52%) (p = 0.003) compared to RA alone. Where hand and foot radiology findings were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive change (p = 0.003). There were no significant differences between groups in smoking history or DMARD/biologic therapy. Conclusions: Increased levels of RA disease activity, severity and RA autoantibodies are demonstrated in patients with RA and co-existent bronchiectasis compared to patients with RA alone, despite lower tobacco exposure. This study demonstrates that BRRA is a more severe systemic disease than RA alone.Arthritis Research UKHEFCECornwall Arthritis TrustNorthcott Devon Medical FoundationDutchy Health CharityNIHR CLR

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

Alpha-1 antitrypsin deficiency; Emphysema; PrevalenceDeficiència d'alfa-1 antitripsina; Emfisema; PrevalençaDeficiencia de alfa-1 antitripsina; Enfisema; PrevalenciaBackground Although bronchiectasis has been recognised as a feature of some patients with Alpha1-Antitrypsin deficiency the prevalence and characteristics are not widely known. We wished to determine the prevalence of bronchiectasis and patient characteristics. The first cohort of patients recruited to the EARCO (European Alpha1 Research Collaboration) International Registry data base by the end of 2021 was analysed for radiological evidence of both emphysema and bronchiectasis as well as baseline demographic features. Results Of the first 505 patients with the PiZZ genotype entered into the data base 418 (82.8%) had a reported CT scan. There were 77 (18.4%) with a normal scan and 38 (9.1%) with bronchiectasis alone. These 2 groups were predominantly female never smokers and had lung function in the normal range. The remaining 303 (72.5%) ZZ patients all had emphysema on the scan and 113 (27%) had additional evidence of bronchiectasis. Conclusions The data indicates the bronchiectasis alone is a feature of 9.1% of patients with the PiZZ genotype of Alpha1-antitrypsin deficiency but although emphysema is the dominant lung pathology bronchiectasis is also present in 27% of emphysema cases and may require a different treatment strategy.The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS)

Bronchiectasis: a model for chronic bacterial infection inducing autoimmunity in rheumatoid arthritis.

ArticleCopyright © 2015 The Authors. Arthritis & Rheumatology is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.Objective: Bronchiectasis (BR) is a risk factor for rheumatoid arthritis (RA). Here we examine the potential of BR in generating rheumatoid factors (RFs) and anti-citrullinated peptide antibodies (ACPA) in patients with BR alone and in patients with BR and RA (BRRA). Methods: We studied 122 patients with BR alone, 50 BRRA, 50 RA without lung disease, with 87 asthma and 79 healthy subjects as controls. RFs were measured by an automated analyzer, and ACPA using CCP2. Fine specificities to citrullinated α-enolase (CEP-1), citrullinated vimentin (cVim) and fibrinogen (cFib) with their arginine control peptides (REP-1, Vim and Fib) measured by ELISA. Results: In the BR patients 39% were ever smokers compared to 42% of the controls. Serum samples from BR patients had an increased frequency of RF (25%; p< 0.05) and 5% to CCP2, 7% to CEP-1, 7% to cVIM (all p=ns) and 12% cFib (p <0.05). There was also a corresponding increase in antibodies to the arginine-containing control peptides in the BR patients; REP-1, 19% (p< 0.01) and Vim, 16% (p<0.05), demonstrating that the ACPA response in BR is not citrulline-specific. Lack of citrulline specificity was further confirmed by absorption studies. In BRRA all ACPA specificities were highly citrulline-specific. Conclusion: Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung. Our study suggests that in the early stages of tolerance breakdown, the ACPA response is not citrulline-specific, but becomes more so in those patients with BR that develop BRRA.Arthritis Research UKEuropean UnionIMI project BTCure7th Framework Programme project Gums and Joint

Digital technologies in bronchiectasis physiotherapy services: a survey of patients and physiotherapists in a UK centre

\ua9 The authors 2024. Introduction We aimed to explore how digital technology is currently used, could be used and how services could be improved in order to optimise bronchiectasis physiotherapy care. Methods Online surveys were designed and distributed amongst people with bronchiectasis and physiotherapists in Northern Ireland. Responses to closed and open question formats were collected and analysed. Results The survey was completed by 48 out of 100 physiotherapists (48%) between January 2020 and January 2021 and by 205 out of 398 people with bronchiectasis (52%) between October 2020 and October 2021. 56% of physiotherapists (27 out of 48) reporting using some type of digital technology to facilitate services, whereas 44% (21 out of 48) reported that they had never used a digital technology in this patient group. When physiotherapists were asked whether they would be likely to use certain remote and/or digital options to deliver follow-up care for airway clearance techniques, most (31–38 out of 48; 65–79%) indicated that they would. Regarding patient responses, most reported that they would use telephone consultation (145 out of 199, 73%) and a smaller proportion were likely to use video consultation (64 out of 199, 32%). The most commonly mentioned theme for improvement amongst patients was follow-ups, while improved access, quality of services and treatments were the most commonly mentioned amongst physiotherapists. Conclusion Despite a large proportion of physiotherapists in this survey reporting no current use of digital technology in bronchiectasis physiotherapy care, there was significant interest and willingness to do so, amongst both physiotherapists and patients. This survey highlighted a range of care areas, specifically follow-up visits, where digital methods could be further explored

Symptoms of COPD in the absence of airflow obstruction are more indicative of pre-COPD than overdiagnosis

Dysfunction of the small airways is a precursor of COPD but is not detectable on standard spirometric testing until significant destruction has occurred. A proportion of COPD patients have an FEV1/FVC less than 0.7 which is greater than the lower limit of normal (LLN), when adjusted for their age and sex. It is not understood whether this group of patients, known as “discordant COPD” are representative of “early COPD” or overdiagnosis. We sought to characterise discordant COPD (disCOPD), using radiology, lung function, serum biomarkers, activity monitoring and quality of life scores, comparing with COPD patients with an FEV1/FVC&lt;0.7 and &lt;LLN and healthy, age-matched controls. Six out of 8 serum biomarkers were significantly different in the disCOPD group versus healthy controls, as were the scores of all 4 QoL questionnaires. Activity monitoring revealed similar levels of sedentary time between the disCOPD group and concordant COPD (conCOPD). CT analysis showed less involvement of small airway dysfunction and emphysema in the disCOPD group versus conCOPD. Collectively, our findings support the hypothesis that disCOPD is a clinically relevant phenomenon that represents a pre-COPD state. Identification of such patients is important for early intervention and management before progression to fully established COPD

Symptoms of COPD in the absence of airflow obstruction are more indicative of pre-COPD than overdiagnosis

Dysfunction of the small airways is a precursor of COPD but is not detectable on standard spirometric testing until significant destruction has occurred. A proportion of COPD patients have an FEV1/FVC less than 0.7 which is greater than the lower limit of normal (LLN), when adjusted for their age and sex. It is not understood whether this group of patients, known as “discordant COPD” are representative of “early COPD” or overdiagnosis. We sought to characterise discordant COPD (disCOPD), using radiology, lung function, serum biomarkers, activity monitoring and quality of life scores, comparing with COPD patients with an FEV1/FVC&lt;0.7 and &lt;LLN and healthy, age-matched controls. Six out of 8 serum biomarkers were significantly different in the disCOPD group versus healthy controls, as were the scores of all 4 QoL questionnaires. Activity monitoring revealed similar levels of sedentary time between the disCOPD group and concordant COPD (conCOPD). CT analysis showed less involvement of small airway dysfunction and emphysema in the disCOPD group versus conCOPD. Collectively, our findings support the hypothesis that disCOPD is a clinically relevant phenomenon that represents a pre-COPD state. Identification of such patients is important for early intervention and management before progression to fully established COPD

COPD-bronchiectasis overlap syndrome

The overlap between chronic obstructive pulmonary disease (COPD) and bronchiectasis is a neglected area of research, and it is not covered by guidelines for clinical practice. Here, we provide a position statement from the BRONCH-UK Consortium that is intended to be of interest to both clinicians and researchers. While we are making recommendations based on expert consensus, one of our aims is to provoke debate. Through discussion of COPD–bronchiectasis overlap, we also aim to promote research in the area, driving improvements in patient care

Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics

\ua9 The authors 2024.Introduction Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369). Methods The ASPEN trial is a global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections), diagnosis confirmed radiologically and ⩾2 exacerbations in the prior 12 months. It was designed to evaluate the impact of two brensocatib doses (10 mg and 25 mg) on exacerbation rate over a 52-week treatment period versus placebo. Comprehensive clinical data, including demographics, disease severity, lung function, Pseudomonas aeruginosa status and quality of life, were collected at baseline. Results 1682 adults from 35 countries were randomised from December 2020 to March 2023. Mean age was 61.3 years and 64.7% were female. ∼70% had moderate-to-severe Bronchiectasis Severity Index (BSI) scores, 29.3% had ⩾3 exacerbations in the prior 12 months and 35.7% were positive for P. aeruginosa. Mean BSI scores were highest in Australia/New Zealand (8.3) and lowest in Latin America (5.9). Overall, the most common aetiology was idiopathic (58.4%). In P. aeruginosa-positive versus P. aeruginosa-negative patients, lung function was lower, with greater long-term macrolide (21.5% versus 14.0%) and inhaled corticosteroid use (63.5% versus 53.9%). There was wide regional variation in long-term antibiotic use in patients with bronchiectasis and P. aeruginosa. Discussion ASPEN baseline characteristics and treatment profiles were representative of a global bronchiectasis population

Psychometrics of HRQoL questionnaires in bronchiectasis: A systematic review and meta-analysis

INTRODUCTION: Understanding the psychometric properties of health related quality of life (HRQoL) questionnaires can help inform selection in clinical trials. OBJECTIVE: To assess the psychometric properties of HRQoL questionnaires in bronchiectasis. METHODS: A literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID), floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials. RESULTS: 166 studies and 12 HRQoL questionnaires were included. The BHQ, LCQ, CAT and SF-36 had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies and the QoL-B, SGRQ, CRDQ and SOLQ had good internal consistency in all domains in the majority of (but not all) studies. The BHQ, SGRQ, LCQ and CAT had good test-retest reliability in all domains reported ((intraclass correlation coefficient) ICC ≥0.7) across all studies and the QoL-B, CRDQ and SOLQ had good test-retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect. CONCLUSION: SGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties, however good psychometric data are growing on bronchiectasis specific HRQoL questionnaires, QoL-B and BHQ. Future studies should focus on the medium-long term test-retest reliability, responsiveness and MCID in these HRQoL questionnaires which show potential in bronchiectasis