Recurrent Exacerbations Research Articles

A quality improvement model to identify undiagnosed heart failure at chronic obstructive pulmonary disease annual reviews

Abstract Introduction Heart failure (HF) is a common comorbidity in people with chronic obstructive pulmonary disease (COPD). The estimated prevalence of HF comorbidity in patients with COPD is up to 40%1. COPD and HF have overlapping symptoms which could delay the diagnosis of HF. Studies have shown that in UK primary care, HF treatment for COPD patients is delayed by almost twelve months compared to patients without COPD2. Early diagnosis and management of HF for COPD patients in primary care could reduce risk of recurrent exacerbation and subsequent hospitalisation. HF screen is not currently emphasised in the primary care COPD annual reviews. NICE guidance for COPD diagnosis mentions the use of serum natriuretic peptides to aid differential diagnosis of HF3. Pharmacists in general practice are the patients’ first point of contact, they are able to take leading roles in the holistic management of long-term conditions such as HF and COPD. Aim Reduce HF related complication including exacerbations and subsequent hospital admissions for COPD patients through early HF identification programme at COPD annual review. Methods Electronic Emis search was conducted on the practice database to identify patients on the COPD register. Patients with existing diagnosis of HF or NT-ProBNP in the last 12 month were excluded. Patients were invited for COPD annual review and screened for HF symptoms (breathlessness, fluid retention, fatigue, lightheadness) as per NICE guidance for HF identification. NT-ProBNP test was added to routine annual blood test for patients experiencing any of the HF symptoms. Patients with elevated NT-ProBNP >400ng/L were referred for further assessment for suspected HF. The project was a small scale service improvement project, it did not require ethical approval, this was confirmed with the Broad Street Health Centre clinical lead. Results Twenty six patients were screened out of 48 (54 %). Six patients (23%) had NT-pro BNP results over 400ng/L and were referred for further investigation for suspected HF. Diagnosis was confirmed for three patients 11%. Two of the newly diagnosed patients had an MRC score of 3, while one had and MRC score of 2. No patients with MRC score 1, 4 or 5 where among the newly diagnosed group. Discussion Results analysis correlates with published data regarding the prevalence of HF in COPD patients. Screening for HF in primary care might be most beneficial for patients with MRC of 2 or 3. Patients with score of 1 might have milder symptoms however annual screening will allow early detection of future deterioration. There were no newly diagnosed patients from the MRC score of 4 and 5 groups as they might have already been diagnosed if their symptoms were related to underlying HF. The three patients diagnosed with HF were treated for HF as per NICE guidance. Patients’ spontaneous feedback was positive regarding the new management approach. Conclusion Pharmacists in general practice can play a dynamic role in early identification of existing co-morbidities while conducting annual long-term conditions reviews. This in return facilitates vital early interventions to improve prognosis and reduce further complications along the way.

Novel CYCLIN-O pathogenic variants in a patient presenting with bronchiectasis secondary to reduced generation of multiple motile cilia.

Reduced generation of multiple motile cilia (RGMC) represents a rare variant of Primary Ciliary Dyskinesia (PCD), associated with CYCLIN-O (CCNO) mutations. We report a novel compound mutation in the CCNO gene in an adult Chinese Singaporean exhibiting chronic productive cough since childhood and recurrent sino-pulmonary infections. Low nasal nitric oxide and bronchiectasis suggests PCD. Bronchoscopy for epithelial and nasal brushings for ciliary studies were repeated after adequate treatment of lower respiratory tract infections. Demonstration of oligo-cilia via transmission electron microscopy, and detection of CCNO mutation through genetic analysis were utilized to diagnose RGMC. Repeated courses of antibiotics including nebulised antibiotics were used to treat recurrent infections and exacerbations. Airway clearance techniques, immunizations and collaboration with otorhinolaryngologist form part of the long-term management. Heightened clinical suspicion and adherence to established diagnostic algorithms are essential for timely recognition of this entity.

Clinical characteristics and prognosis of Talaromycosis marneffei associated immune reconstitution inflammatory syndrome in AIDS patients.

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. Few studies elucidated the clinical features and prognosis of Talaromycosis marneffei (TSM)-associated IRIS in HIV/AIDS patients. The aim of our study was to evaluate the incidence, clinical characteristics, and prognosis of TSM-associated IRIS by retrospectively analyzing the clinical data of HIV/AIDS patients with TSM. A total of 224 HIV/AIDS inpatients with TSM were enrolled, aged between 19 and 81 years. Among them, 86.6% were male and 13.4% were female, of which 24 (10.7%) patients developed IRIS. In IRIS group, the median time from ART initiation to IRIS occurrence was 9.0 days (IQR, 5.0-16.8 days), with 87.5% (21/24) occurring within 2 weeks. Primary clinical manifestations included recurrent fever and exacerbation of pulmonary infection. At the onset of IRIS, 54.2% (13/24) patients were treated with intravenous dexamethasone, and 12.5% (5/24) patients were treated with oral prednisone for 1-3 weeks. No significant differences in baseline characteristics or ART regimens were observed between IRIS and non-IRIS groups; however, patients in IRIS group had higher levels of CRP, CD4+ count, and CD4+/CD8+ ratio than non-IRIS group (equivalent time point: 1-2 weeks after ART initiation) at IRIS onset. The IRIS group exhibited longer hospital stays and higher readmission rates, but equivalent mortality rates compared with non-IRIS group. IRIS is a common complication in HIV/AIDS patients with TSM, often occurring within 2 weeks after ART initiation and exhibiting more pronounced immune reconstitution. The occurrence of IRIS significantly extended the hospitalization duration and increased the rate of readmission but had no influence on the mortality rate.

Biofilm infections of endobronchial valves in COPD patients after endoscopic lung volume reduction: a pilot study with FISHseq

Endoscopic lung volume reduction (ELVR) using endobronchial valves (EBV) is a treatment option for a subset of patients with severe chronic obstructive pulmonary disease (COPD), suffering from emphysema and hyperinflation. In this pilot study, we aimed to determine the presence of bacterial biofilm infections on EBV and investigate their involvement in lack of clinical benefits, worsening symptomatology, and increased exacerbations that lead to the decision to remove EBVs. We analyzed ten COPD patients with ELVR who underwent EBV removal. Clinical data were compared to the microbiological findings from conventional EBV culture. In addition, EBV were analyzed by FISHseq, a combination of Fluorescence in situ hybridization (FISH) with PCR and sequencing, for visualization and identification of microorganisms and biofilms. All ten patients presented with clinical symptoms, including pneumonia and recurrent exacerbations. Microbiological cultures from EBV detected several microorganisms in all ten patients. FISHseq showed either mixed or monospecies colonization on the EBV, including oropharyngeal bacterial flora, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus spp., and Fusobacterium sp. On 5/10 EBV, FISHseq visualized biofilms, on 1/10 microbial microcolonies, on 3/10 single microorganisms, and on 1/10 no microorganisms. The results of the study demonstrate the presence of biofilms on EBV for the first time and its potential involvement in increased exacerbations and clinical worsening in patients with ELVR. However, further prospective studies are needed to evaluate the clinical relevance of biofilm formation on EBV and appropriate treatment options to avoid infections in patients with ELVR.

Oral Bacterial Lysate OM-85: Advances in Pharmacology and Therapeutics.

Bacterial lysates are known for having immunomodulatory properties and have been used mainly for the prevention and treatment of respiratory tract infections (RTIs). However, rigorous studies are needed to confirm the clinical efficacy of bacterial lysates with various bacterial antigen components, preparation methods, administration routes and course of treatment. OM-85, an oral standardized lysate prepared by alkaline lysis of 21 strains from 8 species of common respiratory tract pathogens, is indicated as immunotherapy for prevention of recurrent RTIs and acute infectious exacerbations of chronic bronchitis. OM-85 acts on multiple innate and adaptive immune targets and can restore type 1helper T (Th1)/Th2 balance. Sporadic studies have shown advances in pharmacology and therapeutics of OM-85, and thus an update review is necessary. Literature was retrieved by searching PubMed, Web of science, Embase, CNKI, and Full Text Database of Chinese Medical Journals. New roles of OM-85 were discovered in prevention and treatment of lung cancer, pulmonary tuberculosis, SARS-CoV-2 infection, allergic rhinitis, pulmonary fibrosis, atopic dermatitis, and nephrotic syndrome. Pharmacoeconomic values of OM-85 were demonstrated in prophylaxis and treatment of RTIs, chronic obstructive pulmonary disease, asthma, chronic bronchitis, rhinosinusitis and allergic rhinitis. Two consecutive courses of OM-85 (6 or 12 months apart) could prevent recurrent RTIs in children. Maternal OM-85 treatment could offer benefits for offspring. Product-specific response was observed. The efficacy of OM-85 may be associated with patient's characteristics (eg, severity of the disease, age, immune response pattern, malignancy risk stratification). OM-85 can improve effectiveness of standard care for some primary diseases, and carry significant pharmacoeconomic implications. The benefits shown by OM-85 in vitro and in vivo, when extrapolated to humans, are exciting but also require caution. Individualized treatment may need to be considered. It is necessary to compare the efficacy and safety of various bacterial lysate preparations.

Population Pharmacokinetic Modeling of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients with Cystic Fibrosis.

Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF. One hundred fifty-five pediatric and adult participants with CF receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted using nonlinear mixed-effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) for different dosing regimens. Estimated creatinine clearance, and total or lean body weight, affected the pharmacokinetics of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-h infusion achieved higher PTA than a 0.5-h infusion for all participants. Estimated breakpoints (the respective minimum inhibitory concentration (MIC) up to which ≥90% of patients are predicted to reach a PK/PD target) were two- to four-fold higher in pediatric participants receiving a 3-h vs. 0.5-h infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA. Standard dosing regimens fail to achieve specific MIC targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time beta-lactam therapeutic drug monitoring.

Outcome of Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) in a Tertiary Care Hospital

Background: Patients with chronic obstructive pulmonary disease (COPD) may suffer from recurrent exacerbations, with a worsening of symptoms and reduction in lung function that may not be recovered in a small proportion of patients. Exacerbations of COPD are associated with increased morbidity and mortality. Objectives: The objectives of the study were to find out the in-hospital outcome of patients admitted with COPD exacerbation Methods: This prospective observational study was conducted in the Department of Medicine, Shere Bangla Medical College Hospital, Barisal during the period of January 2022 to December 2022. 42 known patients with COPD exacerbation admitted in medicine unit during the study period were enrolled in the study by convenient sampling. COPD with bronchogenic carcinoma, with bronchiectasis and with ischaemic heart disease were excluded from the study. All patients were examined regularly for cough, sputum, grading of dyspnoea, tracheal tug, prominence of accessory muscles, sleep disturbance, frequency of inhaled β-2 agonist therapy per day for 7 days. After 7 days follow up, patients were categorized into-improved, when it fulfills the following GOLD criteria or not improved. After processing all available information Statistical analysis was done using SPSS for windows version 22. Results: The mean±SD age of the patients was 66.3±10.0 years with a range of 46-85 years.There were 37(88.1%) male patients and 5(11.9%) female patients. The mean±SD duration of illness of the patients was 9.24±4.05 years with a range of 2-15 years. The median duration was 10 years. Tracheal tag, prominence of accessory muscles of respiration, sleep disturbance, cyanosis, and loss of consciousness was present in 95.2%, 95.2%, 71.4%, 28.60% and 9.5% patients respectively. X-ray chest P-A view showed that 88.1% patients had the diagnosis of only COPD, 2.4% had COPD with cardiomegaly and 2.4% had COPD with cor-pulmonale and 7.1% normal X-ray finding. ECG finding showed that 9.5% patients had Cor pulmonale with COPD, 11.9% had sinus tachycardia, 4.8% had. RVH, 2.4% had p pulmonale with sinus tachycardia. The mean±SD oxygen saturation of the patients was 92.10±5.27% with a range of 72-95%. The median saturation was 94%. The mean±SD length of hospital stay was 5.21±1.18 days with a range of 3-7 days. The median length of hospital stay was 5 days. 39(92.9%) patients were improved and discharged from the hospital and 3(7.1%) patients died. Conclusion: The mean length of hospital stay was about 5 days. 92.9% of the cases, the symptoms of exacerbations of COPD subside within 10 days with standard regimen of treatment and in-hospital mortality was 7.1%

CLINICAL MANAGEMENT OF CHRONIC ORANGUTAN RESPIRATORY DISEASE SYNDROME IN THREE ADULT MALE BORNEAN ORANGUTANS (PONGO PYGMAEUS).

Orangutan respiratory disease syndrome (ORDS) is a disease unique to orangutans (Pongo sp), characterized by chronic bacterial infection and inflammation of any region or combination of regions of the respiratory tract, including the sinuses, air sacs, cranial bones, airways, and lung parenchyma. Aggressive early intervention during a first episode may prevent progression to chronic disease. However, in the setting of an established chronic disease, intermittent acute exacerbations are associated with worsening symptoms and increased infection and inflammation. ORDS is ultimately fatal due to loss of respiratory function resulting from chronic structural damage. Utilizing potentially lifelong medications to slow the progression of chronic, destructive inflammation in the respiratory tract, chronic treatment is aimed at stabilizing the animals' respiratory function, decreasing the frequency of recurrent exacerbations, and improving their general well-being. Three adult male Bornean orangutans (Pongo pygmaeus) housed at an orangutan rehabilitation and reintroduction center in Indonesia have long histories of recurrent respiratory disease. Each underwent CT scans confirming ORDS with chronic airway disease prior to initiation of a long-term treatment protocol. Based on data-driven medical management of bronchiectasis in humans, the three orangutans have been treated with long-term combination regimens of oral azithromycin, nebulized salbutamol, and nebulized hypertonic saline. Follow-up CT scans in all three animals at least 1 yr following treatment initiation showed improvements throughout their respiratory tracts. The duration of each exacerbation period decreased, and the orangutans have longer symptom-free periods compared to before the start of treatment. At an average of 5 yr into the long-term treatment protocol, all three orangutans are thriving. Chronic medical management of ORDS modeled after human treatment of bronchiectasis has been efficacious in these three orangutans and encourages further study of this approach.

Therapeutic Management of Bronchiectasis in Children and Adolescents: A Concise Narrative Review.

Introduction: Bronchiectasis, characterized by airway dilation, mucus hypersecretion, and recurrent exacerbations, is increasingly recognized in children and adolescents. Recent guidelines from the European Respiratory Society (ERS) and Thoracic Society of Australia and New Zealand (TSANZ) emphasize early diagnosis and optimized management. This review explores therapeutic strategies for pediatric bronchiectasis. Materials and methods: Our review involved a comprehensive search of English-language literature in the PubMed and EMBASE databases until December 2023, focusing on observational studies, interventions, reviews, and guidelines in pediatric bronchiectasis. Results: Management strategies encompass airway clearance techniques, mucoactive agents, pulmonary rehabilitation, bronchodilators and inhaled corticosteroids tailored to individual needs and age-appropriate techniques. Antibiotics play key roles in preventing exacerbations, eradicating pathogens, and managing acute exacerbations, which are guided by culture sensitivities and symptoms. Long-term antibiotic prophylaxis, particularly macrolides, aims to reduce exacerbations, although concerns about antibiotic resistance persist. Vaccinations, including pneumococcal and influenza vaccines, are crucial for preventing infections and complications. Surgery and lung transplantation are reserved to severe, refractory cases after failure of medical therapies. Conclusions: The optimal management of pediatric bronchiectasis requires a multidisciplinary approach, including physiotherapy, pharmacotherapy, and vaccinations, tailored to individual needs and guided by evidence-based guidelines. Further research is needed to refine diagnostic and therapeutic strategies and improve outcomes for affected children and adolescents.

Biomarker defined infective and inflammatory asthma exacerbation phenotypes in hospitalized adults: clinical impact and phenotype stability at recurrent exacerbation

Objective Acute exacerbations (AEs) of asthma are heterogeneous in terms of triggers, outcomes, and treatment response. This study investigated biomarker defined infective and inflammatory AE phenotypes in hospitalized adult asthma patients, and their impact on clinical outcomes and phenotype stability at AE recurrence. Method Patients with asthma admitted with an AE between January 2010 and December 2011 with a 3-year follow-up were retrospectively studied. AEs were categorized into infective (CRP >10 mg/L) vs non-infective, eosinophilic (blood eosinophils ≥ 0.2 × 109 cells/L) vs non-eosinophilic, and viral (CRP >10 to <40 mg/L) vs bacterial (CRP ≥40 mg/L) phenotypes. Clinical impact of the index AE, the risk and time to a second AE and AE phenotype stability were analyzed using Kaplan-Meier survival curves and McNamar’s test. Result 294 asthma patients were included: 47% had infective AE with a longer length of stay than non-infective AE (2.0 vs. 1.0 days, p = 0.01). The proportion of patients with eosinophilic AEs was evenly distributed across infective and non-infective AE (40% vs. 46%), although more patients with viral had eosinophilia than bacterial AE (46% vs. 26%). During follow-up, 18% had recurrent AE; with a higher risk in viral AE than bacterial AE (25% vs. 8%, p = 0.02). Both inflammatory and infective AE phenotype were stable at recurrent AE. Conclusion AE phenotyping in hospitalized asthma patients, based on CRP and blood eosinophils, revealed prolonged hospital stay in infective AEs and a higher risk of recurrent AE requiring hospitalization in viral versus bacterial AEs. Moreover, infective, and inflammatory AE phenotypes were rather stable at recurrent AE. Our results suggest a role for biomarker guided phenotyping of AEs of asthma.

Wellness and its correlation with vitamin D

Abstract Background: Wellness encompasses various interconnected physical, mental, and social dimensions beyond the traditional definition of health. Vitamin D deficiency is a widespread nutritional deficiency, with a prevalence of 80%–90% in India, and is often under-diagnosed and under-treated worldwide. While vitamin D is classically known for its role in bone health, it also has significant extra-skeletal effects, including maintaining muscle function, immunity, anti-inflammatory activity, and cell proliferation and differentiation. Recent studies have linked vitamin D deficiency to fatigue, myalgia, low-energy fractures, muscle weakness, anxiety, and depression. Furthermore, it is implicated in the development of type 1 and type 2 diabetes mellitus (DM) and hypertension. Vitamin D deficiency is also associated with recurrent exacerbations of bronchial asthma, autoimmune diseases, and malignancies. Addressing this deficiency can substantially enhance patient well-being, prevent serious health outcomes, and improve overall wellness. Aim: This study aims to investigate the relationship between wellness and vitamin D levels. Materials and Methods: This prospective nonrandomized therapeutic study was conducted at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India, and included 246 participants from July 2021 to December 2022. The study included patients reporting generalized weakness, fatigue, myalgia, low mood, lack of motivation, and decreased interest in life by the inclusion and exclusion criteria. Their serum vitamin D levels were tested. Participants with vitamin D deficiency (&lt;30 ng/mL) completed a pre-structured well-being questionnaire and received vitamin D supplementation for 10 weeks. Wellness in these patients was evaluated using a pre-structured post-supplementation well-being questionnaire. Results: The results revealed that out of 324 patients included in the study, 253 (78.1%) were deficient in vitamin D. The highest deficiency rate was among those aged 18–35 years (85.5%). Vitamin D deficiency was more prevalent in females (79.5%, 167 out of 210 females) compared with males (75.4%, 86 out of 114 males). The paired t test results showed a significant increase in post-test vitamin D levels (t = -219.922, P &lt; 0.001) and a significant decrease in post-test Fatigue Assessment Scores (t = 31.328, P &lt; 0.001) and Fatigue Severity Scores (t = 33.066, P &lt; 0.001). Additionally, there was a significant improvement in post-test World Health Organization-Five Well-Being Index (WHO-5) scores (t = -28.495, P &lt; 0.001) and Warwick–Edinburgh Mental Well-being Scores (WEMWBS; t = -28.996, P &lt; 0.001). Karl Pearson’s correlation coefficient indicated that post-supplementation vitamin D levels were positively correlated with post-supplementation Fatigue Assessment Scores (r = 0.315) and Fatigue Severity Scores (r = 0.334). Conversely, they negatively correlated with the WHO-5 Well-being Index (r = -0.322) and the WEMWBS (r = -0.294). Conclusion: This study concludes that wellness is directly correlated with vitamin D levels. There is a significant improvement in the Fatigue Assessment Scale, Fatigue Severity Scale, WHO-5 Well-being Index, WEMWBS, and overall physical, mental, and social wellness following vitamin D supplementation in patients, both with and without comorbidities (hypertension and DM).

Is there any interplay between human gut microbiota and upper airway susceptibility to recurrent respiratory papillomatosis exacerbations?

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Recurrent respiratory papillomatosis is a long-term disease caused by HPV 6 and 11, but there is still noconsensus on the factors that may influence its course.&lt;/br&gt;&lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of the study is the analysis of the recurrent activity of respiratory papillomatosis measured by the number ofsurgeries and recent disease activity, as well as an interview regarding intestinal symptoms.&lt;/br&gt;&lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; Our study involved 73 patients with confirmed papillomatosis (39 men, 34 women). The mainvariables of crucial importance for the severity of papilloma disease were: age of onset, number of operations, and currentdisease activity. Variables important for the analysis of the impact of intestinal dysbiosis on the course of papillomatosis wereas follows: intestinal symptoms and the number of antibiotic courses in the last year. The main outcome measure in this studywas the relationship between papilloma activity and indicators of intestinal microflora status.&lt;/br&gt;&lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Our results showed that diet had a statistically significant effect on the last disease activity measured by the intervalrecurrence of RRP (P = 0.005). The remaining variables did not affect the number of surgeries performed during the patient’slifetime or the current RRP status.&lt;/br&gt;&lt;br&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The acquired knowledge may contribute to further work on the discovery of the relationship between the stateof the intestinal microbiota and the course of recurrence of respiratory papillomatosis infection in patients with recurrentrespiratory papillomatosis.&lt;/br&gt;

Subcellular location of L1 retrotransposon-encoded ORF1p, reverse transcription products, and DNA sensors in lupus granulocytes

BackgroundSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with an unpredictable course of recurrent exacerbations alternating with more stable disease. SLE is characterized by broad immune activation and autoantibodies against double-stranded DNA and numerous proteins that exist in cells as aggregates with nucleic acids, such as Ro60, MOV10, and the L1 retrotransposon-encoded ORF1p.ResultsHere we report that these 3 proteins are co-expressed and co-localized in a subset of SLE granulocytes and are concentrated in cytosolic dots that also contain DNA: RNA heteroduplexes and the DNA sensor ZBP1, but not cGAS. The DNA: RNA heteroduplexes vanished from the neutrophils when they were treated with a selective inhibitor of the L1 reverse transcriptase. We also report that ORF1p granules escape neutrophils during the extrusion of neutrophil extracellular traps (NETs) and, to a lesser degree, from neutrophils dying by pyroptosis, but not apoptosis.ConclusionsThese results bring new insights into the composition of ORF1p granules in SLE neutrophils and may explain, in part, why proteins in these granules become targeted by autoantibodies in this disease.

Pulmonary Nocardiosis in a patient with recurrent COPD exacerbations

Pulmonary nocardiosis is a rare infection with a high mortality rate. We present a case of an elderly male with severe COPD treated with repeated courses of prednisone and highlight specific factors predisposing to a Nocardia infection. We review literature data and advocate for early invasive testing to direct management. We underline the role of early bronchoscopy in this select population given its safety and potential diagnostic yield.

An Exploratory Study of Physician Decision-Making When Treating Uncontrolled COPD.

Current guidelines recommend triple therapy maintenance inhalers for patients with recurrent exacerbations of chronic obstructive pulmonary disease (COPD); however, these maintenance therapies are underutilized. This study aimed to understand how physicians make COPD treatment decisions, and how combination maintenance therapies are utilized in a real-world setting. This exploratory, hypothesis-generating, non-interventional study used a cross-sectional online survey that was administered to a sample of practicing physicians in the United States. The survey included five fictitious vignettes detailing common symptoms experienced by patients with COPD. Survey questions included factors physicians consider in their decisions, and perceived barriers to prescribing treatments. Repeated measures multivariable analyses were conducted to evaluate how likely physicians were to switch to triple therapy versus no change to patient's current maintenance therapy or change to another maintenance therapy. In total, 200 physicians completed the survey. Cost of treatment and patient access to treatment were reported as the most common barriers physicians consider in their prescribing decisions. Physicians were more likely to switch a patient's maintenance inhaler to triple therapy versus no change to maintenance inhaler if they considered the patient's history of new symptoms, insurance status, and clinical guidelines in their decision. Physicians with more experience treating patients with COPD, and those who treat more patients with COPD per week, were more likely to switch to triple therapy versus no change to maintenance inhaler. This study demonstrates the complexity of factors that can influence physicians' decisions when prescribing treatments for patients with COPD, including considerations of treatment cost, patient access and adherence, patient comorbidities, efficacy of current treatment, clinical guidelines, and provider's level of experience treating COPD. Further research may help elucidate the relative importance of the factors influencing physicians' decisions and inform what types of decision-support tools would be most beneficial.

Comparative microbiome analysis in cystic fibrosis and non-cystic fibrosis bronchiectasis.

Bronchiectasis is a condition characterized by abnormal and irreversible bronchial dilation resulting from lung tissue damage and can be categorized into two main groups: cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). Both diseases are marked by recurrent infections, inflammatory exacerbations, and lung damage. Given that infections are the primary drivers of disease progression, characterization of the respiratory microbiome can shed light on compositional alterations and susceptibility to antimicrobial drugs in these cases compared to healthy individuals. To assess the microbiota in the two studied diseases, 35 subjects were recruited, comprising 10 NCFB and 13 CF patients and 12 healthy individuals. Nasopharyngeal swabs and induced sputum were collected, and total DNA was extracted. The DNA was then sequenced by the shotgun method and evaluated using the SqueezeMeta pipeline and R. We observed reduced species diversity in both disease cohorts, along with distinct microbial compositions and profiles of antimicrobial resistance genes, compared to healthy individuals. The nasopharynx exhibited a consistent microbiota composition across all cohorts. Enrichment of members of theBurkholderiaceaefamily and an increased Firmicutes/Bacteroidetes ratio in the CF cohort emerged as key distinguishing factors compared to NCFB group.Staphylococcus aureusand Prevotella shahii also presented differential abundance in the CF and NCFB cohorts, respectively, in the lower respiratory tract. Considering antimicrobial resistance, a high number of genes related to antibiotic efflux were detected in both disease groups, which correlated with the patient's clinical data. Bronchiectasis is associated with reduced microbial diversity and a shift in microbial and resistome composition compared to healthy subjects. Despite some similarities, CF and NCFB present significant differences in microbiome composition and antimicrobial resistance profiles, suggesting the need for customized management strategies for each disease.

Bronquiectasias: enfoque diagnóstico y terapéutico

Bronchiectasis is a chronic inflammatory disease of the airways that is manifested by chronic cough, mucosal o mucopurulent bronchorrhea, and recurrent exacerbations. Its etiology is varied, but it is essential within its study to try to identify the cause to avoid progressive lung damage, a product of the so-called “vicious circle” with recurrent infections, inflammation and permanent structural damage. The diagnosis is clinical and must be confirmed by performing a high-resolution chest computed tomography. Therapeutic management should be aimed at controlling infection and bronchial inflammation, as well as managing associated complications and comorbidities.

Long-Term Erythromycin Treatment Alters the Airway and Gut Microbiota: Data from Chronic Obstructive Pulmonary Disease Patients and Mice with Emphysema

Introduction: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. Methods: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. Results: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. Conclusion: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.

A Roadmap for Using Causal Inference and Machine Learning to Personalize Asthma Medication Selection.

Inhaled corticosteroid (ICS) is a mainstay treatment for controlling asthma and preventing exacerbations in patients with persistent asthma. Many types of ICS drugs are used, either alone or in combination with other controller medications. Despite the widespread use of ICSs, asthma control remains suboptimal in many people with asthma. Suboptimal control leads to recurrent exacerbations, causes frequent ER visits and inpatient stays, and is due to multiple factors. One such factor is the inappropriate ICS choice for the patient. While many interventions targeting other factors exist, less attention is given to inappropriate ICS choice. Asthma is a heterogeneous disease with variable underlying inflammations and biomarkers. Up to 50% of people with asthma exhibit some degree of resistance or insensitivity to certain ICSs due to genetic variations in ICS metabolizing enzymes, leading to variable responses to ICSs. Yet, ICS choice, especially in the primary care setting, is often not tailored to the patient's characteristics. Instead, ICS choice is largely by trial and error and often dictated by insurance reimbursement, organizational prescribing policies, or cost, leading to a one-size-fits-all approach with many patients not achieving optimal control. There is a pressing need for a decision support tool that can predict an effective ICS at the point of care and guide providers to select the ICS that will most likely and quickly ease patient symptoms and improve asthma control. To date, no such tool exists. Predicting which patient will respond well to which ICS is the first step toward developing such a tool. However, no study has predicted ICS response, forming a gap. While the biologic heterogeneity of asthma is vast, few, if any, biomarkers and genotypes can be used to systematically profile all patients with asthma and predict ICS response. As endotyping or genotyping all patients is infeasible, readily available electronic health record data collected during clinical care offer a low-cost, reliable, and more holistic way to profile all patients. In this paper, we point out the need for developing a decision support tool to guide ICS selection and the gap in fulfilling the need. Then we outline an approach to close this gap via creating a machine learning model and applying causal inference to predict a patient's ICS response in the next year based on the patient's characteristics. The model uses electronic health record data to characterize all patients and extract patterns that could mirror endotype or genotype. This paper supplies a roadmap for future research, with the eventual goal of shifting asthma care from one-size-fits-all to personalized care, improve outcomes, and save health care resources.

Predictor of recurrent exacerbations in pediatric asthma

BACKGROUND Asthma imposes a heavy morbidity burden during childhood. Severe persistent asthma significantly increases patients’ risk of exacerbations, hospital admissions, and mortality and often substantially impairs their quality of life. This study aimed to identify high-risk patients for exacerbation recurrence using spirometric parameters. METHODS A prospective cohort study involving patients with asthma aged 6–15 years was conducted at the principal children’s hospital in Mekong Delta, Vietnam, from June 2020 to June 2022. Demographic, clinical, and lung function characteristics of the patients were collected. Spirometry measurement parameters were utilized as predictive factors for the short-term asthma exacerbation recurrence. RESULTS Among all patients (mean age of 9.5 years old), 10.4% experienced recurrent exacerbations. FEV1, FVC, FEV1/FVC, FEF25–75, FEF25–75/FVC, and PEF, gradually decreased with increasing exacerbation severity (p&lt;0.01). All patients showed a positive bronchodilator responsiveness (BDR), with a mean value of 16.85 (3.00)%, which was significantly different between the severe and non-severe asthma groups (20.53 [2.83] versus 16.00 [2.35], p&lt;0.001). After adjusting in multivariable logistic regression, a BDR ≥20% was identified as the sole independent factor associated with an increased risk of asthma exacerbation recurrence (aOR 6.95, 95% CI 1.08–44.75, p = 0.041). CONCLUSIONS A high BDR can serve as a predictor of acute asthma exacerbation recurrence.