Development of a core outcome set for physiotherapy trials in adults with bronchiectasis (the COS-PHyBE study): A Delphi study and consensus meeting.

Background: Physiotherapy is recommended for bronchiectasis management, but there is disparity in evidence supporting its use. This is partly because of inconsistency and poor reporting of outcomes in available studies. A Core Outcome Set (COS) may improve trial consistency and decrease reporting bias. This study aimed to develop a COS for physiotherapy clinical trials in adults with bronchiectasis. Methods: A comprehensive list of outcomes was developed using a systematic review and qualitative semi-structured interviews with patients with bronchiectasis and physiotherapists.An international two-round online Delphi survey was conducted. Outcomes scored 7-9 (crucial) by ≥ 70 % of participants and 1-3 (not that important) by ≤ 15 % of participants from each stakeholder in the Likert scale were nominated for inclusion in the COS. Nominated outcomes and those considered crucial by only one of the stakeholders' groups were further discussed and voted in an international consensus meeting. Results: A list of 137 outcomes was generated; 104 from literature and 33 from interviews. A Delphi survey containing 59 outcomes was completed by 171 participants from 20 countries. After the consensus meeting, representatives agreed on seven outcomes: health-related quality of life, respiratory symptoms, physical functioning, emotional and psychological functioning, fatigue, adherence to treatment, and functional exercise capacity. Conclusion: A minimum set of seven outcomes are recommended to be included as measurements in future trials evaluating physiotherapy interventions for bronchiectasis.

Kartagener syndrome with pectus excavatum and upper lobar bronchiectasis.

Primary Ciliary Dyskinesia (PCD) is a rare autosomal recessive disorder caused by impaired ciliary function. The incidence of PCD is 1 in 20,000 births. Kartagener's syndrome (KS), a subtype of PCD, is distinguished by the presence of situs inversus. KS occurs in about 1 in 32,000 to 40,000 births. Characterized by a triad of situs inversus totalis, sinusitis, and typically lower lobe bronchiectasis, Kartagener's syndrome presents with distinct radiological features, which are explored in this case study. We report on an adolescent male with Kartagener's syndrome, manifesting atypical bronchiectasis in the left upper lobe, leading to a bilateral lung transplant, and severe pectus excavatum requiring surgical correction. This case documents a male patient with concurrent Kartagener's syndrome and pectus excavatum, supporting a previously explored, albeit theoretical association between these conditions.

Potential New Inflammatory Markers in Bronchiectasis: A Literature Review.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as "precision medicine". With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease's natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials.

Phenotypical characteristics of nontuberculous mycobacterial infection in patients with bronchiectasis.

BACKGROUND: The global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis. METHODS: A retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020. Clinical, laboratory, pulmonary function, and radiological data were compared between patients with a positive or negative NTM culture. RESULTS: Compared to the NTM-negative group (n=677), the NTM-positive group (n=94) was characterized (P ≤0.05 for all) by older age, greater proportion of females, and higher rates of gastroesophageal reflux disease and muco-active medication use; lower body mass index, serum albumin level, and lymphocyte and eosinophil counts; lower values of forced expiratory volume in one second, forced vital capacity, and their ratio, and lower diffusing lung capacity for carbon monoxide; higher rates of bronchiectasis in both lungs and upper lobes and higher number of involved lobes; and more exacerbations in the year prior bronchoscopy. On multivariate analysis, older age (OR 1.05, 95% CI 1.02-1.07, P=0.001), lower body mass index (OR 1.16, 95% CI 1.16-1.07, P <0.001), and increased number of involved lobes (OR 1.26, 95% CI 1.01-1.44, P=0.04) were associated with NTM infection. CONCLUSIONS: Patients with bronchiectasis and NTM pulmonary infection are more likely to be older and female with more severe clinical, laboratory, pulmonary function, and radiological parameters than those without NTM infection. This phenotype can be used for screening patients with suspected NTM disease.

Computed tomography imaging and clinical significance of bacterium-positive pulmonary tuberculosis complicated with diabetes.

BACKGROUND: The increasing prevalence of tuberculosis (TB) and diabetes on a global scale poses a significant health challenge, particularly due to their co-occurrence, which amplifies the severity, recurrence and mortality rates associated with both conditions. This highlights the need for further investigation into their inter-relationship. AIM: To explore the computed tomography (CT) imaging and clinical significance of bacterium-positive pulmonary TB (PTB) combined with diabetes. METHODS: There were 50 patients with bacterium-positive PTB and diabetes, and 50 with only bacterium-positive PTB. The latter were designated as the control group. The CT imaging of the two groups of patients was compared, including lesion range, shape, density and calcification. RESULTS: No significant differences were observed in age, gender, smoking and drinking history, high blood pressure, hyperlipidemia and family genetic factors between the groups. However, compared to the patients diagnosed solely with simple bacterium-positive PTB, those with concurrent diabetes showed a wider range of lesions and more complex and diverse morphology on CT images. Among them, intrapulmonary tuberculosis lesions were often accompanied by manifestations of pulmonary infection, such as cavity formation and bronchiectasis. At the same time, diabetes-related signs were often seen on CT images, such as pulmonary infection combined with diabetic pulmonary lesions. Logistic regression analysis identified age and medical history as significant factors influencing the degree of pulmonary infection and CT imaging outcomes in patients with both TB and diabetes. This suggests that older age and specific medical histories may increase the risk or severity of pulmonary damage in these patients. CONCLUSION: CT imaging reveals more complex lesions in PTB patients with diabetes, emphasizing the need for careful evaluation and comprehensive analysis to enhance diagnostic accuracy.

Development of allergic bronchopulmonary aspergillosis in a patient with nontuberculous mycobacterial-pulmonary disease successfully treated with dupilumab: A case report and literature review.

Pulmonary manifestations in patients with allergic bronchopulmonary aspergillosis (ABPA) and nontuberculous mycobacterial-pulmonary disease (NTM-PD) include bronchiectasis and mucus plugging. A 68-year-old woman, treated with antibiotics and inhaled corticosteroids for NTM-PD and asthma, presented with fever and wheezing. ABPA was diagnosed based on laboratory findings (elevated peripheral blood eosinophil counts and serum total IgE levels and positive Aspergillus-specific IgE and IgG) and imaging observation of a high-attenuation mucus plug. Systemic prednisolone was avoided to prevent NTM-PD progression. Dupilumab, a monoclonal antibody that blocks IL-4/13, was introduced to improve the clinical findings. Herein, we discuss the pathophysiological mechanisms underlying this rare comorbidity.

Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study.

BACKGROUND: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. METHODS: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. RESULTS: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis. CONCLUSION: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.

BACKGROUND: Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome. OBJECTIVES: To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation. METHODS: Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab. RESULTS: Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation. CONCLUSION: Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.

The causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional Mendelian randomization study.

Background: Several observational studies suggested an association between rheumatoid arthritis (RA) and bronchiectasis. Nevertheless, the presence of a causal relationship between these conditions is yet to be determined. This study aimed to investigate whether genetically predicted RA is associated with the risk of bronchiectasis and vice versa. Methods: We obtained RA genome-wide association study (GWAS) data from FinnGen consortium, and bronchiectasis GWAS data from IEU Open GWAS project. Univariate Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) estimation as the main method. Furthermore, bidirectional and replication MR analysis, multivariate MR (MVMR), Mediation analysis, and sensitivity analyses were conducted to validate the findings. Results: In the UVMR analysis, the IVW results revealed that RA had an increased risk of bronchiectasis (OR = 1.18, 95% CI = 1.10-1.27; p = 2.34 × 10-6). In the reverse MR analysis, no evidence of a causal effect of bronchiectasis on the risk of RA was detected. Conversely, in the replication MR analysis, RA remained associated with an increased risk of bronchiectasis. Estimates remained consistent in MVMR analyses after adjusting for the prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Immunosuppressants were found to mediate 58% of the effect of the RA on bronchiectasis. Sensitivity analyses confirmed the stability of these associations. Conclusion: This study demonstrated a positive causal relationship between RA and an increased risk of bronchiectasis, offering insights for the early prevention of bronchiectasis in RA patients and shedding new light on the potential role of immunosuppressants as mediators in promoting the effects of RA on bronchiectasis.

Kartagener's Syndrome: A Case Series.

Kartagener's syndrome is an uncommon autosomal recessive ciliary dyskinesia. It combines a triad comprised of bronchiectasis, chronic sinusitis, and situs inversus. This work aims to describe the clinical and paraclinical aspects of primary ciliary dyskinesia using Kartagener's syndrome as a model and to highlight the difficulties of confirming the diagnosis in our context. We report four observations (three boys and one girl with an average age of 10 years) of Kartagener's syndrome collected in the department of pediatric pneumo-allergology. Chronic bronchorrhea and otorhinolaryngological manifestations were found in all cases. Signs of neonatal respiratory distress syndrome were found in only one case. One child had dysmorphic facial features suggestive of Noonan's syndrome and conductive hearing loss. Digital hippocratism was found in half of the cases, along with pulmonary crackles and heart sounds perceived on the right. A chest CT scan showed bronchiectasis in all patients and necrotic adenopathy suggestive of tuberculosis in one case. Sinus imaging showed an appearance of pansinusitis. All children had abdominal situs inversus with dextrocardia. They had received antibiotic therapy with amoxicillin-clavulanic acid associated with respiratory physiotherapy. The girl had benefited from a right lobectomy with a follow-up of 18 months and a good evolution. In light of these four observations, Kartagener's syndrome is a rare disease but can be compatible with normal life if the treatment is done early. However, in our context, the difficulty of confirming the diagnosis explains its delay with the risk of progression of pulmonary lesions.

Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks.

Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

Primary Ciliary Dyskinesia Due to Compound Heterozygous Variants in CFAP221 with Obstructive Azoospermia: Young's Syndrome May Be a Phenotype of Primary Ciliary Dyskinesia.

We report the case of a 42-year-old man with bronchiectasis who had a history of infertility treatment for obstructive azoospermia. Young's syndrome was suspected based on the triad of obstructive azoospermia, sinusitis, and bronchiectasis. He had normal electron microscopy findings, normal nasal nitric oxide levels (116 nL/min), and no situs inversus. However, we found compound heterozygous variants in CFAP221. This led to a diagnosis of primary ciliary dyskinesia (PCD). Distinguishing PCD from Young's syndrome in patients with the triad of obstructive azoospermia, sinusitis, and bronchiectasis is challenging. Young's syndrome may be a phenotype of PCD.

Screening for primary immune deficiency among patients with bronchiectasis.

INTRODUCTION: To assess frequency and methods of PID (primary immune deficiency) screening among patients with bronchiectasis by pneumologists in clinical practice. METHODS: All the patients hospitalized in the department of pneumology of the Poitiers University Hospital between April 2013 and April 2020 with a diagnosis of bronchiectasis on chest computerized tomography were included. Patients aged 70 and over and those with already known PID were excluded. Primary endpoint was the proportion of patients having had serum immunoglobulin (Ig) assay and serum protein electrophoresis (SPE) analysis. Secondary endpoints were factors associated with prescription of SPE and/or Ig assay, proportion of patients with newly diagnosed PID and their characteristics and factors associated with repeated courses of antibiotics. RESULTS: Among the 133 patients included, 43% had SPE+Ig assay, 34% SPE only and 23% neither. The proportion of patients with asthma was higher in the "SPE+Ig assay" group (33.3%) compared to the "SPE only" (11.1%) and the "Neither SPE nor Ig assay" groups (6.4%) (P=0.002). Four patients were newly diagnosed for PID of whom 3 had subclass IgG deficiency. Factors associated with repeated courses of antibiotics were generalized bronchiectasis (P=0.02) and asthma (P=0.04). CONCLUSION: PID is underscreened by pneumologists among patients with bronchiectasis. Association of SPE+Ig assay+IgG subclass assay appears as the most accurate combination.

Rheumatoid arthritis extra-articular lung disease: new insights on pathogenesis and experimental drugs.

INTRODUCTION: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature. AREAS COVERED: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients. EXPERT OPINION: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.

Bronchiectasis.

Non-cystic fibrosis bronchiectasis, a condition that remains relatively underrecognized, has garnered increasing research focus in recent years. This scientific interest has catalyzed advancements in diagnostic methodologies, enabling comprehensive clinical and molecular profiling. Such progress facilitates the development of personalized treatment strategies, marking a significant step toward precision medicine for these patients. Bronchiectasis poses significant diagnostic challenges in both clinical settings and research studies. While computed tomography (CT) remains the gold standard for diagnosis, novel alternatives are emerging. These include artificial intelligence-powered algorithms, ultra-low dose chest CT, and magnetic resonance imaging (MRI) techniques, all of which are becoming recognized as feasible diagnostic tools. The precision medicine paradigm calls for refined characterization of bronchiectasis patients by analyzing their inflammatory and molecular profiles. Research into the underlying mechanisms of inflammation and the evaluation of biomarkers such as neutrophil elastase, mucins, and antimicrobial peptides have led to the identification of distinct patient endotypes. These endotypes present variable clinical outcomes, necessitating tailored therapeutic interventions. Among these, eosinophilic bronchiectasis is notable for its prevalence and specific prognostic factors, calling for careful consideration of treatable traits. A deeper understanding of the microbiome's influence on the pathogenesis and progression of bronchiectasis has inspired a holistic approach, which considers the multibiome as an interconnected microbial network rather than treating pathogens as solitary entities. Interactome analysis therefore becomes a vital tool for pinpointing alterations during both stable phases and exacerbations. This array of innovative approaches has revolutionized the personalization of treatments, incorporating therapies such as inhaled mannitol or ARINA-1, brensocatib for anti-inflammatory purposes, and inhaled corticosteroids specifically for patients with eosinophilic bronchiectasis.

Las bronquiectasias no fibrosis quística han atraído una creciente atención en investigación. Este interés científico ha catalizado avances en las metodologías de diagnóstico, permitiendo realizar perfiles clínicos y moleculares integrales. Este progreso facilita el desarrollo de estrategias de tratamiento personalizadas y marca un paso significativo hacia la medicina de precisión.Desde el punto de vista diagnóstico, las bronquiectasias plantean desafíos importantes en entornos clínicos y de investigación. Si bien la TC es el gold standard, están surgiendo nuevas alternativas. Entre ellas, algoritmos de inteligencia artificial, TC de tórax de dosis ultrabajas y técnicas de resonancia magnética.La medicina de precisión aboga por la caracterización de pacientes mediante análisis de perfiles inflamatorios y moleculares. Las investigaciones sobre mecanismos subyacentes de inflamación y la evaluación de biomarcadores como la elastasa de neutrófilos, mucinas y péptidos antimicrobianos, han llevado a la identificación de endotipos de pacientes. Estos endotipos exhiben resultados clínicos variables, requiriendo intervenciones terapéuticas personalizadas. La bronquiectasia eosinofílica destaca por su prevalencia y factores pronósticos específicos, exigiendo consideración de los rasgos tratables.Una comprensión profunda de la influencia del microbioma en la patogénesis y progresión de las bronquiectasias inspira un enfoque holístico. Considera el multibioma como una red microbiana interconectada, no entidades solitarias. El análisis del interactoma se convierte en una herramienta vital para identificar alteraciones durante fases estables y exacerbaciones.Este conjunto de enfoques innovadores revoluciona la personalización de los tratamientos, incorporando terapias como manitol inhalado o ARINA-1, brensocatib con fines antiinflamatorios y corticosteroides inhalados específicos para pacientes con bronquiectasias eosinofílicas.

Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza-A Territory-Wide Study.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.