-
Medicine Dec 2023This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in...
This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in patients with acute exacerbations of bronchiectasis (noncystic fibrosis) to guide clinical treatment and improve patients' quality of life and prognosis. This prospective study included 54 patients with acute exacerbation and 46 clinically stable patients admitted to the Respiratory and Critical Care Medicine Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to July 2022. Sputum was subjected to routine microbiological tests, and bronchoalveolar lavage fluid (BALF) samples were subjected to microbiological tests and mNGS of BALF before empirical antibiotic therapy. Serum inflammatory markers (white blood cell count, interleukin-6, procalcitonin, and C-reactive protein) were measured. In addition, we evaluated the pathogen of mNGS and compared the airway microbiome composition of patients with acute exacerbation and control patients. The mean age of our cohort was 56 ± 15.2 years. Eighty-nine patients had positive results by mNGS. There was a significant difference in the detection of viruses between the groups (χ2 = 6.954, P < .01). The fungal species Candida albicans, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly more common in patients with acute exacerbations (χ2 = 5.98, P = .014). The bacterial species Acinetobacter baumannii, Mycobacterium tuberculosis, Haemophilus influenzae, Haemophilus parahaemolyticus, Abiotrophia defectiva, and Micromonas micros were significantly more prevalent in patients with acute exacerbations (χ2 = 4.065, P = .044). The most common bacterial species isolated from the sputum and BALF samples of patients with acute exacerbation was A. baumannii. Chlamydia psittaci was found in 4 patients. In addition, of 77 patients with negative sputum culture, 66 had positive results by mNGS, demonstrating the increased sensitivity and accuracy of mNGS. Patients with acute exacerbation of bronchiectasis tend to have mixed infections in the lower respiratory tract. The frequency of viruses, fungi, and Mycoplasma was higher in these patients. Our findings suggest that mNGS could be used to identify pathogenic microorganisms in these patients, increasing the effectiveness of antibiotic therapy.
Topics: Humans; Adult; Middle Aged; Aged; Prospective Studies; Quality of Life; Bronchiectasis; Microbiota; Respiratory System; Anti-Bacterial Agents; High-Throughput Nucleotide Sequencing; Sensitivity and Specificity
PubMed: 38115299
DOI: 10.1097/MD.0000000000036519 -
Annals of the American Thoracic Society Oct 2023It can be challenging for healthcare professionals (HCPs) to prescribe inhaled therapy for patients with chronic obstructive pulmonary disease (COPD) because of the... (Review)
Review
It can be challenging for healthcare professionals (HCPs) to prescribe inhaled therapy for patients with chronic obstructive pulmonary disease (COPD) because of the multiple individual and combinations of inhaled medications available in numerous delivery systems. Guidance on the selection of an inhaled delivery system has received limited attention compared with the emphasis on prescribing the class of the inhaled molecule(s). Although numerous recommendations and algorithms have been proposed to guide the selection of an inhaled delivery system for patients with COPD, no specific approach has been endorsed in COPD guidelines/strategies or by professional organizations. To provide recommendations for an inhaler selection strategy at initial and follow-up appointments, we examined the impact of patient errors using handheld inhalers on clinical outcomes and performed a focused narrative review to consider patient factors (continuity of the inhaled delivery system, cognitive function, manual function/dexterity, and peak inspiratory flow) when selecting an inhaled delivery system. On the basis of these findings, five questions are proposed for HCPs to consider in the initial selection of an inhaler delivery system and three questions to consider at follow-up. We propose that HCPs consider the inhaled medication delivery system as a unit and to match appropriate medication(s) with the unique features of the delivery system to individual patient factors. Assessment of inhaler technique and adherence together with patient outcomes/satisfaction at each visit is essential to determine whether the inhaled medication delivery system is providing benefits. Continued and repeated education on device features and correct technique is warranted to optimize efficacy.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Nebulizers and Vaporizers; Pharmaceutical Preparations; Patient Satisfaction; Administration, Inhalation; Bronchodilator Agents
PubMed: 37499210
DOI: 10.1513/AnnalsATS.202304-384CME -
Allergology International : Official... Jan 202427-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic...
BACKGROUND
27-Hydroxycholesterol (27-HC) derived from sterol 27-hydroxylase (CYP27A1) has pro-inflammatory biological activity and is associated with oxidative stress and chronic inflammation in COPD. However, the role of regulation of CYP27A1- 27-HC axis in asthma is unclear. This study aimed to elucidate the contribution of the axis to the pathophysiology of asthma.
METHODS
House dust mite (HDM) extract was intranasally administered to C57BL/6 mice and the expression of CYP27A1 in the airways was analyzed by immunostaining. The effect of pre-treatment with PBS or CYP27A1 inhibitors on the cell fraction in the bronchoalveolar lavage fluid (BALF) was analyzed in the murine model. In vitro, BEAS-2B cells were treated with HDM and the levels of CYP27A1 expression were examined. Furthermore, the effect of 27-HC on the expressions of E-cadherin and ZO-1 in the cells was analyzed. The amounts of RANTES and eotaxin from the 27-HC-treated cells were analyzed by ELISA.
RESULTS
The administration of HDM increased the expression of CYP27A1 in the airways of mice as well as the number of eosinophils in the BALF. CYP27A1 inhibitors ameliorated the HDM-induced increase in the number of eosinophils in the BALF. Treatment with HDM increased the expression of CYP27A1 in BEAS-2B cells. The administration of 27-HC to BEAS-2B cells suppressed the expression of E-cadherin and ZO-1, and augmented the production of RANTES and eotaxin.
CONCLUSIONS
The results of this study suggest that aeroallergen could enhance the induction of CYP27A1, leading to allergic airway inflammation and disruption of the airway epithelial tight junction through 27-HC production.
Topics: Animals; Mice; Pyroglyphidae; Mice, Inbred C57BL; Asthma; Dermatophagoides pteronyssinus; Lung; Bronchoalveolar Lavage Fluid; Inflammation; Allergens; Cadherins; Disease Models, Animal
PubMed: 37607853
DOI: 10.1016/j.alit.2023.08.005 -
Advances in Therapy Jul 2023Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC).... (Review)
Review
INTRODUCTION
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
METHODS
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
RESULTS
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
CONCLUSION
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
Topics: Humans; Eosinophils; Anti-Asthmatic Agents; Biological Products; Asthma; Leukocyte Count; Eosinophilia; Double-Blind Method
PubMed: 37233876
DOI: 10.1007/s12325-023-02514-0 -
Seminars in Immunopathology Jan 2024The lungs serve as the primary organ for respiration, facilitating the vital exchange of gases with the bloodstream. Given their perpetual exposure to external... (Review)
Review
The lungs serve as the primary organ for respiration, facilitating the vital exchange of gases with the bloodstream. Given their perpetual exposure to external particulates and pathogens, they possess intricate protective barriers. Cellular adhesion in the lungs is robustly maintained through tight junctions, adherens junctions, and desmosomes. Furthermore, the pulmonary system features a mucociliary clearance mechanism that synthesizes mucus and transports it to the outside. This mucus is enriched with chemical barriers like antimicrobial proteins and immunoglobulin A (IgA). Additionally, a complex immunological network comprising epithelial cells, neural cells, and immune cells plays a pivotal role in pulmonary defense. A comprehensive understanding of these protective systems offers valuable insights into potential pathologies and their therapeutic interventions.
Topics: Humans; Lung; Animals; Mucociliary Clearance; Respiratory Mucosa; Tight Junctions; Cell Adhesion; Mucus
PubMed: 38451292
DOI: 10.1007/s00281-024-01003-y -
Annals of Allergy, Asthma & Immunology... Nov 2023Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have...
BACKGROUND
Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations.
OBJECTIVE
To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA.
METHODS
CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment.
RESULTS
A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients.
CONCLUSION
Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT03373045.
Topics: Adult; Humans; Asthma; Omalizumab; Biological Products; Anti-Asthmatic Agents
PubMed: 37506846
DOI: 10.1016/j.anai.2023.07.017 -
The Journal of Allergy and Clinical... Apr 2024Severe asthma is associated with significant morbidity and mortality despite the maximal use of inhaled corticosteroids and additional controller medications, and has a... (Review)
Review
Severe asthma is associated with significant morbidity and mortality despite the maximal use of inhaled corticosteroids and additional controller medications, and has a high economic burden. Biologic therapies are recommended for the management of severe, uncontrolled asthma to help to prevent exacerbations and to improve symptoms and health-related quality of life. The effective management of severe asthma requires consideration of clinical heterogeneity that is driven by varying clinical and inflammatory phenotypes, which are reflective of distinct underlying disease mechanisms. Phenotyping patients using a combination of clinical characteristics such as the age of onset or comorbidities and biomarker profiles, including blood eosinophil counts and levels of fractional exhaled nitric oxide and serum total immunoglobulin E, is important for the differential diagnosis of asthma. In addition, phenotyping is beneficial for risk assessment, selection of treatment, and monitoring of the treatment response in patients with asthma. This review describes the clinical and inflammatory phenotypes of asthma, provides an overview of biomarkers routinely used in clinical practice and those that have recently been explored for phenotyping, and aims to assess the value of phenotyping in severe asthma management in the current era of biologics.
Topics: Humans; Anti-Asthmatic Agents; Biological Products; Quality of Life; Asthma; Eosinophils; Biomarkers
PubMed: 38280454
DOI: 10.1016/j.jaip.2024.01.023 -
American Journal of Respiratory and... Aug 2023
Topics: Humans; COVID-19; SARS-CoV-2; Respiratory System; Respiratory Distress Syndrome; Respiration, Artificial
PubMed: 37311259
DOI: 10.1164/rccm.202302-0223LE -
Paediatric Drugs Nov 2023Severe asthma in children and adolescents exerts a substantial health, financial, and societal burden. Severe asthma is a heterogeneous condition with multiple clinical... (Review)
Review
Severe asthma in children and adolescents exerts a substantial health, financial, and societal burden. Severe asthma is a heterogeneous condition with multiple clinical phenotypes and underlying inflammatory patterns that might be different in individual patients. Various add-on treatments have been developed to treat severe asthma, including monoclonal antibodies (biologics) targeting inflammatory mediators. Biologics that are currently approved to treat children (≥ 6 years of age) or adolescents (≥ 12 years of age) with severe asthma include: anti-immunoglobulin E (omalizumab), anti-interleukin (IL)-5 (mepolizumab), anti-IL5 receptor (benralizumab), anti-IL4/IL13 receptor (dupilumab), and antithymic stromal lymphopoietin (TSLP) (tezepelumab). However, access to these targeted treatments varies across countries and relies on few and crude indicators. There is a need for better treatment stratification to guide which children might benefit from these treatments. In this narrative review we will assess the most recent developments in the treatment of severe pediatric asthma, as well as potential biomarkers to assess treatment efficacy for this patient population.
Topics: Humans; Child; Adolescent; Anti-Asthmatic Agents; Asthma; Biological Products
PubMed: 37658954
DOI: 10.1007/s40272-023-00589-4 -
Cross-System Integration of Respiration and Deglutition: Function, Treatment, and Future Directions.Dysphagia Aug 2023Swallowing occurs preferentially in the expiratory phase of the quiet breathing cycle and at mid-to-low tidal volume. This coordinative pattern imparts important... (Review)
Review
Swallowing occurs preferentially in the expiratory phase of the quiet breathing cycle and at mid-to-low tidal volume. This coordinative pattern imparts important biomechanical advantages to swallowing and airway protection and facilitate laryngeal elevation, laryngeal vestibular and vocal fold closure, and cricopharyngeal sphincter opening. This preferred coordinative relationship between breathing and swallowing is impaired in a variety of patient populations, including head and neck cancer survivors with dysphagia. We developed a training protocol to re-establish more optimal phasing of swallowing with breathing in these patients with striking outcomes, including reduced swallowing physiological impairments and improved airway protection. This motivated us to continue to refine and expand this training protocol and develop new assistive technologies for swallowing monitoring outside of the lab. In this review, we highlight the origins of our optimal respiratory-swallowing coordination hypothesis, describe the biomechanical advantages it provides, carefully describe our training protocol and findings, and chart a course for the next phase of this work. Our overall goal is to harness technology combined with carefully constructed learning paradigms to improve the lives of patients with impaired respiratory-swallowing coordination consequent to a variety of pathologies including head and neck cancer and degenerative neurological conditions such as Parkinson's disease.
Topics: Humans; Deglutition; Respiration; Deglutition Disorders; Larynx; Head and Neck Neoplasms
PubMed: 36378345
DOI: 10.1007/s00455-022-10538-x