Management Of Airway Diseases Research Articles

Cystic fibrosis pathogens persist in the upper respiratory tract following initiation of elexacaftor/tezacaftor/ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a Pseudomonas-dominant, Staphylococcus-dominant, and mixed dominance cluster. Shannon's diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. Pseudomonas spp. abundance was significantly reduced post-ETI, but eradication was not observed. Staphylococcus spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of Pseudomonas spp., Staphylococcus spp., and Serratia spp. in the sputum. Pseudomonas spp. and Staphylococcus spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of Pseudomonas spp. in the sinuses following ETI therapy. We also show that Staphylococcus spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant Staphylococcus aureus (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.

Treatable traits in asthma during pregnancy: a call for a shift towards a precision-based management approach.

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy.

Neural Mechanisms Underlying the Coughing Reflex.

Breathing is an intrinsic natural behavior and physiological process that maintains life. The rhythmic exchange of gases regulates the delicate balance of chemical constituents within an organism throughout its lifespan. However, chronic airway diseases, including asthma and chronic obstructive pulmonary disease, affect millions of people worldwide. Pathological airway conditions can disrupt respiration, causing asphyxia, cardiac arrest, and potential death. The innervation of the respiratory tract and the action of the immune system confer robust airway surveillance and protection against environmental irritants and pathogens. However, aberrant activation of the immune system or sensitization of the nervous system can contribute to the development of autoimmune airway disorders. Transient receptor potential ion channels and voltage-gated Na+ channels play critical roles in sensing noxious stimuli within the respiratory tract and interacting with the immune system to generate neurogenic inflammation and airway hypersensitivity. Although recent studies have revealed the involvement of nociceptor neurons in airway diseases, the further neural circuitry underlying airway protection remains elusive. Unraveling the mechanism underpinning neural circuit regulation in the airway may provide precise therapeutic strategies and valuable insights into the management of airway diseases.

Application of aortic allograft in trachea transplantation

The use of tracheal implants for tracheal reconstruction remains a challenge in thoracic medicine due to the complex structure of the trachea in mammalian organisms, including smooth muscles, cartilage, mucosa, blood vessels, cilia, and other tissues, and the difficulty in achieving tracheal regeneration using implants from either allografts or synthetic biomaterials. This project used the Lee-Sung strain pig, a swine breed local to Taiwan, as the experimental subject. The aorta of the pig was harvested, decellularized to form the scaffold, and transplanted into the trachea of allogeneic pigs together with growth factors. Postoperative physiological function and tissue changes were observed. The postoperative physiological parameters of the LSP were monitored, and they were sacrificed after a certain period to observe the pathological changes in the tracheal epithelial cells and cartilages. Overall, six LSP tracheal transplantations were performed between March 4, 2020, and March 10, 2021. These included aortic patch anastomosis for pig 1 and aortic segmental anastomosis for pigs 2-6. The shortest and longest survival periods were 1 day and 147 days, respectively. Excluding the pig that survived for only 1 day due to a ruptured graft anastomosis, all other subjects survived for over 1 month on average. In this study, we grafted a decellularized porcine aorta into a recipient pig with a tracheal defect. We found cryopreservation of the allogeneic aorta transplantation was a feasible and safe method for the management of airway disease, and immunosuppressants were unnecessary during the treatment course.

Direct Visualization and Quantitative Imaging of Small Airway Anatomy In Vivo Using Deep Learning Assisted Diffractive OCT.

In vivo imaging and quantification of the microstructures of small airways in three dimensions (3D) allows a better understanding and management of airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). At present, the resolution and contrast of the currently available conventional optical coherence tomography (OCT) imaging technologies operating at 1300 nm remain challenging to directly visualize the fine microstructures of small airways in vivo. We developed an ultrahigh-resolution diffractive endoscopic OCT at 800 nm to afford a resolving power of 1.7 µm (in tissue) with an improved contrast and a custom deep residual learning based image segmentation framework to perform accurate and automated 3D quantification of airway anatomy. The 800-nm diffractive OCT enabled the direct delineation of the structural components in the small airway wall in vivo. We further first demonstrated the 3D anatomic quantification of critical tissue compartments of small airways in sheep using the automated segmentation method. The deep learning assisted diffractive OCT provides a unique ability to access the small airways, directly visualize and quantify the important tissue compartments, such as airway smooth muscle, in the airway wall in vivo in 3D. These pilot results suggest a potential technology for calculating volumetric measurements of small airways in patients in vivo.

A survey and stakeholder group prioritised key systematic review questions in airways disease.

Priority setting is important for healthcare research. The Cochrane Airways Group wanted to prioritise topics for systematic reviews across all chronic respiratory diseases with limited resources and according to latest Cochrane policy.The objective was to prioritise 10 reviews of importance to the public (patients, carers, healthcare professionals and researchers) from a patient survey. We convened a stakeholder group of patients, carers, healthcare professionals and representatives from charities. We conducted an online survey to collect uncertainties about the treatment and management of respiratory disease from the public. Uncertainties were ranked by the stakeholder group, and scoping searches refined the uncertainties into systematic review questions. We received 147 survey responses. We removed duplicates and blank responses and asked the stakeholder group to rank 100 uncertainties. The first round of voting produced a list of 29 topics and the second round resulted in 12 uncertainties. These uncertainties were scoped with literature searches and teased out further into systematic review topics. We identified 3 Cochrane reviews to update, 8 new review topics, and 3 evidence gaps. We successfully convened a stakeholder group and prioritised a list of uncertainties in the treatment and management of airways diseases that had been identified by patients and the public.

Application of exhaled nitric oxide detection in the diagnosis, treatment and management of chronic airway diseases: current status and prospects

Airway inflammation is the most important pathological basis of chronic airway diseases. The detection and evaluation of airway inflammation is helpful for the diagnosis, treatment and management of airway diseases. Exhaled nitric oxide is the most widely used noninvasive airway inflammation detection technique in recent years, which provides a simple and quick reference for the diagnosis and management of chronic airway diseases, but there are still some controversies and deficiencies. This paper briefly expounds the biological significance of exhaled nitric oxide and detecting technique, summarizes the clinical application and the deficiencies of exhaled nitric oxide detection. In the future, with the further researchers on technology and the accumulation of application experiences, the detection technology of exhaled nitric oxide will play a more significant role in the accurate management of chronic airway diseases.

Diagnostic Accuracy of Liquid Biomarkers in Airway Diseases: Toward Point-of-Care Applications.

BackgroundLiquid biomarkers have shown increasing utility in the clinical management of airway diseases. Salivary and blood samples are particularly amenable to point-of-care (POC) testing due to simple specimen collection and processing. However, very few POC tests have successfully progressed to clinical application due to the uncertainty and unpredictability surrounding their diagnostic accuracy.ObjectiveTo review liquid biomarkers of airway diseases with well-established diagnostic accuracies and discuss their prospects for future POC applications.MethodologyA literature review of publications indexed in Medline or Embase was performed to evaluate the diagnostic accuracy of liquid biomarkers for chronic obstructive pulmonary disease (COPD), asthma, laryngopharyngeal reflux (LPR), and COVID-19.ResultsOf 3,628 studies, 71 fulfilled the inclusion criteria. Sputum and blood eosinophils were the most frequently investigated biomarkers for the management of asthma and COPD. Salivary pepsin was the only biomarker with a well-documented accuracy for the diagnosis of LPR. Inflammatory blood biomarkers (e.g., CRP, D-dimers, ferritin) were found to be useful to predict the severity, complications, and mortality related to COVID-19 infection.ConclusionMultiple liquid biomarkers have well-established diagnostic accuracies and are thus amenable to POC testing in clinical settings.

Use of inhaled antibiotics among Danish patients with cystic fibrosis

BackgroundInhaled antibiotics are an important part of cystic fibrosis (CF) airway disease management and should be individualized to fit the microorganism and match patient needs. To investigate the implementation of personalized treatment, this study mapped the use of different types of inhaled antibiotics and adherence patterns.MethodsWe performed individual structured interviews in a cross‐sectional study at the CF Centre in Copenhagen, Denmark. Patients with CF older than 15 years attending clinical consultations were included. Clinical data were obtained from centralized databases.ResultsAmong 149 participants, 107 (72%) had indication for treatment with inhaled antibiotics. In this group, 97 (91%) reported the use of inhaled antibiotics within the last 12 months. Change from one inhaled antibiotic to another during that period was reported by 31 (29%), and 17 (25%) with Pseudomonas aeruginosa had used off‐label antibiotics. Adherence to a minimum of one daily dose of antibiotic was reported by 78%, while adherence to all daily doses was 28 percentage points lower. Skipping inhalations was due to side effects and doubt about the effect in less than 5% of cases.ConclusionChange of inhaled antibiotics and use of off‐label antibiotics for inhalation were common and side effects were a rare cause of nonadherence. This suggests satisfactory implementation of the principle of tailored antibiotic inhalation prescription in the Copenhagen CF population. Adherence to at least one daily inhalation dose was markedly higher than adherence to multiple daily inhalations.

ACO (Asthma–COPD Overlap) Is Independent from COPD: The Case Against

Over the last decade interest has been shown in people with symptomatic lung disease who have features both of COPD and asthma. In this review we examine how COPD and asthma are defined and examine clinical characteristics of people defined by researchers as having asthma-COPD overlap (ACO). We look at pathological and physiological features along with symptoms and consider the impact of each diagnosis upon therapeutic management. We highlight challenges in the diagnosis and management of airway disease and the various phenotypes that could be part of ACO, in so doing suggesting ways for the clinician to manage patients with features of both asthma and COPD.

The lengths of trachea and main bronchus in Chinese\xa0Shanghai population

The knowledge of airway length is the theoretical basis in the diagnosis and management of airway disease. The objective of this study is to measure the length of trachea and left and right main bronchus in Chinese Shanghai population. A total of 153 consecutive adult patients with minor pulmonary disease in Xinhua hospital were enrolled for bronchoscopy examination. Measurements were conducted on head and neck neutral position and height, weight and age for each patient were recorded either. Student t test and multiple linear regression was used to compare means between males and females and to analyze correlation among height, weight, sexual dimorphism and the lengths of the trachea and bronchus. The lengths of the trachea and left main bronchus are significantly different between male and female patients (P < 0.01), but not for the lengths of right main bronchus between man and woman. Multiple linear regression analysis showed that height but not sexual dimorphism and weight correlated with the lengths of the trachea and right main bronchus. The lengths of the trachea and left main bronchus are significantly longer in males than in females. Moreover, height but not sexual dimorphism and weight influenced the length of airway.

A new dimension of success in the management of airway disease in children with neurological deficit

ObjectivesAnomalies of the larynx and trachea can cause respiratory distress in infants and older children. Depending on its nature, degree and extent of the disease invasive open surgery is indicated. Non-airway-related co-morbidities increase the challenges in its treatment. Neurological deficit poses a great challenge as it is associated with hypotonia and causes diminished laryngeal coordination. The definition of success in treatment of laryngotracheal disease has always focused on the post-operative functional outcomes: breathing, voice swallowing. The aim of this study is to describe a new dimension of success in the management of laryngotracheal disease in children with moderate neurological deficit, where the expected functional gain is less than in otherwise healthy children. MethodsThis retrospective observational study includes all patients who have undergone open reconstructive airway surgery between 2012 and 2017. Control patients without neurological deficit and cases with moderate neurological deficit were included. Functional outcome data was obtained from clinical records and two questionnaires were filled in by the parents of the children: one the pediatric voice-handicap index (pVHI) and a quality of life questionnaire. ResultsThirty-two children were included of which ten had moderate neurological deficit. Both groups revealed post-operatively an improvement in the functional outcomes: breathing, voice and swallowing, however, as expected, a trend was observed towards less functional improvement in children with neurological deficit. Both groups reveal a remarkable gain in quality of life (QoL). ConclusionIndicating the QoL to be an unidentified, dimension of success in the management of laryngotracheal disease in children with moderate neurological deficit.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Expression of ACE2 in airways: Implication for COVID-19 risk and disease management in patients with chronic inflammatory respiratory diseases.

Coronavirus disease 2019 (COVID‐19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been a rising international cause of morbidity and mortality. Angiotensin‐converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS‐CoV‐2 and suggested to be a limiting factor for viral entry at the initial infection stage. Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS‐CoV‐2. The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID‐19 risk and affect the management of primary airway diseases. In this review, we focus on the cutting‐edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID‐19. We also discuss the management of airway diseases, including asthma, COPD, allergic rhinitis, and rhinosinusitis in the era of COVID‐19.

Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro

Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.

February Podcast: ERS/TSANZ statement on management of airways diseases in pregnant women.

As part of the February issue, the European Respiratory Journal presents the latest in its series of podcasts. Deputy Chief Editor James Chalmers interviews Peter G. Middleton (University of Sydney, Sydney, Australia) about the European Respiratory Society and the Thoracic Society of Australia and New Zealand’s new statment on the management of reproduction and pregnancy in women with airways diseases published in this issue.

Measuring lung function in airways diseases: current and emerging techniques

Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these...

Assessment of metered-dose inhaler technique: A study at the pulmonology clinic of a tertiary hospital in the Free State, South Africa

Background . Poor pressurised metered-dose inhaler (pMDI) technique remains a challenge in the management of airway diseases. Objectives. To assess pMDI technique among respiratory outpatients and identify the main indications for pMDI use and factors associated with improper use. Methods. is was a prospective, quantitative descriptive study conducted at the adult respiratory clinic of Universitas Academic Hospital in Bloemfontein, South Africa. A convenience sample of 100 participants was used. Each participant was interviewed and required to demonstrate the use of a placebo pMDI, either alone or with a large-volume spacer. Inhaler technique was evaluated according to the UK Inhaler Group standard for inhaler therapy. Results. Chronic obstructive pulmonary disease and asthma were the most common indications for pMDI use. Of the 100 participants, 97 preferred a pMDI without a spacer (pMDI alone) and three preferred using the inhaler with a spacer. In the pMDI-alone group, 13 participants (13.4%) demonstrated correct technique and 65 (67%) made more than one error. Conclusion. Poor inhaler technique is common among respiratory outpatients. Every contact with the patient should be an opportunity to reinforce correct pMDI

Treatable traits in acute exacerbations of chronic airway diseases.

Acute exacerbations of chronic airway disease are common occurrences that cause a major burden of illness. Acute exacerbations are associated with impaired health status, increased lung function decline, hospitalization and increased risk of death. Exacerbation avoidance is a major priority. Despite this goal, exacerbations continue to occur and the need for effective models of care that optimize patient outcomes are urgently needed. ‘Treatable Traits’ is an approach to personalized medicine that has been proposed for the management of airway diseases. The treatable traits approach allows for the recognition of clinically important, identifiable and treatable disease characteristics, followed by targeted and individualized treatment interventions to address each trait. We review the literature relating to treatable traits in airway diseases; in particular, those traits that can predict exacerbations and approaches to management that aim to prevent exacerbations by using a treatable traits model of care. We propose this approach as a potentially useful model of care to both prevent and manage acute exacerbations.

Updates on bronchoscopic management of airway disease

Tracheobronchial surgery is one of the most challenging fields in thoracic surgery. Tremendous effort has been made to ensure that surgical resection and reconstruction of the tracheobronchial tree can be performed safely, and minimally‐invasive video assisted thoracoscopic surgery pioneers have recently pushed the limit for certain airway procedures. However, surgical resection of the diseased airway is often not feasible or contraindicated due to the nature of the disease or advanced malignancies. In the present, we focus on the endobronchial treatment of adult airway diseases and the latest updates.