Nonasthmatic Eosinophilic Bronchitis Research Articles

Eosinophilic bronchitis – Chronic cough with a treatable trait

Eosinophilia in sputum is an important finding in patients with chronic cough, as it identifies a treatable trait with available therapy that is well tolerated and can be effective. While most patients have airway hyperresponsiveness or airway obstruction which define asthma, an important number of cases lack these features of bronchoconstriction but sputum induction still demonstrates excess eosinophilia, indicating eosinophilic bronchitis without asthma. Unfortunately, this test is largely limited to research centers and speciality cough clinics, but associated measures of allergic airway inflammation can be used to support the diagnosis. While the mechanisms that initiate and drive non-asthmatic eosinophilic bronchitis (NAEB) are not well understood, there is emerging evidence that eosinophils and inflammatory mediators are important contributors of nerve sensitivity, a hallmark of chronic cough. Inhaled steroids form the major treatment used in non-asthmatic eosinophilic bronchitis (NAEB). Novel targeted therapies for asthma known as biologics are likely to be tried in the common and debilitating condition of chronic cough, while their efficacy in NAEB is yet to be seen.

Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.

Eosinophilic asthma (EA) and non-asthmatic eosinophilic bronchitis (EB) share similar eosinophilic airway inflammation. Unlike EA, EB did not present airway hyperresponsiveness or airflow obstruction. We aimed to compare the mechanism underlying the different manifestations between EA and EB via sputum transcriptomics analysis. Induced-sputum cells from newly physician-diagnosed EA, EB patients, and healthy controls (HCs) were collected for RNA sequencing. Bulk RNA sequencing was performed using sputum cells from patients with EA (n = 18), EB (n = 15) and HCs (n = 28). Principal component analysis revealed similar gene expression patterns in EA and EB. The most differentially expressed genes in EB compared with HC were also shared by EA, including IL4, IL5 IL13, CLC, CPA3, and DNASE1L3. However, gene set enrichment analysis showed that the signatures regulating macrophage activation were enriched in EA compared to EB. Sputum cells were profiled using single-cell RNA sequencing. FABP4+ macrophages, SPP1+ macrophages, FCN1+ macrophages, dendritic cells, T cells, B cells, mast cells, and epithelial cells were identified based on gene expression profiling. Analysis of cell-cell communication revealed that interactions between FCN1+ macrophages and other cells were higher in EA than in EB. A wealth of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) interactions between FCN1+ macrophages and other cells have been shown in EA. The gene expression levels of EREG, TGFBI, and VEGFA in FCN1+ macrophages of EA were significantly higher than those of EB. Furthermore, signatures associated with the response to TGF-β, cellular response to VEGF stimulus and developmental cell growth were enriched in FCN1+ macrophages of EA compared to those of EB. FCN1+ macrophage activation associated with airway remodeling processes was upregulated in EA compared to that in EB, which may contribute to airway hyperresponsiveness and airflow obstruction.

Non-asthmatic eosinophilic bronquitis review. A systematic review of current treatment options.

Non-asthmatic eosinophilic bronchitis is characterized by persistent dry or less productive cough and bronchial eosinophilia without airway obstruction or bronchial hyperreactivity. It is primarily a chronic disease in which some patients have clinical and pathophysiological relapses while others progress to asthma or chronic obstructive pulmonary disease. It accounts for 5 to 30% of cases referred for chronic cough. Exposure to common inhalants and occupational sensitizers has been proposed as a possible cause of the disease, but its etiology and underlying mechanisms are uncertain. Some features were similar to those of asthma, such as airway eosinophilia, level of inflammatory mediators and airway remodeling. Nevertheless, there are differences in airway pathophysiology, such as the location of airway inflammation and levels of IL-13 and PGE-2. Sputum cell count is the “gold standard” test for diagnosis, and other biomarkers, such as exhaled nitric oxide, could support the diagnosis. A systematic review of treatments for the disease has been done. Although inhaled corticosteroids are the primary treatment, the accurate dose, the kind of corticosteroid, and the treatment time remain unknown. Treatment duration is inversely correlated with relapse rate. Increased doses of inhaled corticosteroids, oral corticosteroids and leukotriene receptor antagonists are recommended in perseverance disease. Anti IL-5 biologic could be promising in this disease. There is a requirement for studies that investigate biomarkers for diagnosis and prognosis and randomized controlled studies for second-line treatments.

Chronic cough and refractory chronic cough: An important distinction

Cough is the most common concern for which patients in the United States seek medical attention. Cough is typically classified according to its duration: acute cough (<3 weeks), subacute cough (3‐8 weeks), and chronic cough (>8 weeks). The vast majority of cases of acute cough in patients are due to an acute viral upper respiratory tract infection (common cold) and are self limited. Subacute cough is often due to a prolonged postviral cough. Once a cough meets the definition of chronic, it becomes likely that the cough is due to one or more treatable underlying etiologies: upper airway cough syndrome (formerly, postnasal drip syndrome), asthma and non-asthmatic eosinophilic bronchitis, and gastroesophageal reflux disease. Refractory chronic cough (RCC) refers to chronic cough that persists despite adequate therapeutic trials aimed at the known causes of chronic cough. The term cough hypersensitivity syndrome has recently been introduced to stress the concept that RCC is a distinct disease entity due to vagal hyperactivity causing hypersensitivity of the cough reflex. No medications have ever been approved for chronic cough or RCC in the United States and most of the world. Thus, physicians are limited to the use of off-label medications for their patients with this chronic and often debilitating condition. However, recent insights into the mechanisms of cough have resulted in multiple molecules currently being evaluated as potential antitussives. Among these, furthest along in the drug development pipeline are the P2X3-antagonists, of which, gefapixant has completed phase III trials, and camlipixant is currently in phase III studies.

Evaluation and management of chronic cough in adults

Background: Chronic cough (CC), a cough that lasts > 8 weeks, has an overall prevalence of 5‐11% in adults, peaking between 60 and 80 years of age. Of the 15% of patients who remain undiagnosed or refractory to treatment, two thirds are women. Objective: The objective was to present an updated evidence-based algorithmic approach for evaluating and managing CC, with emphasis on treatment modalities for refractory CC. Methods: A literature search was conducted of medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from January 2022 to June 2023, on the evaluation and management of CC. Results: The initial assessment should be limited to a detailed history, physical examination, chest radiograph, spirometry, exhaled nitric oxide, blood eosinophil count, and measurement of cough severity and quality of life by using validated instruments. The top diagnoses to consider are asthma, chronic obstructive pulmonary disease, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airway cough syndrome. Additional studies are only obtained when red flags are present or the patient fails to respond after avoidance of high-risk factors, e.g., smoking and angiotensin-converting enzyme inhibitors, and 4‐6 weeks of empiric treatment for the most likely respiratory and gastrointestinal diseases. When diagnostic tests and/or specific directed treatments fail to control CC, low-dose morphine (preferred), gabapentin, pregabalin, and/or cough control therapy are recommended. Non-narcotic purinergic 2×3 (P2×3) receptor antagonists, gafapixant and campilixant, are currently being studied for CC. Conclusion: For the evaluation and management of patients with CC, clinicians should use an algorithmic approach and identify “red flags,” reduce high-risk factors, and use empiric treatment for the five top diagnoses before extensive diagnostic testing. Current treatment for refractory cough is limited to symptomatic management.

Dijagnostika i terapija hroničnog kašlja

A cough that lasts for more than 8 weeks in adults (those older than 15 years) and more than 4 weeks in children is considered chronic and poses a significant health problem, as it can lead to feelings of fatigue, sleep disturbances, hoarseness, disruption of daily activities, vomiting, and often in women, even incontinence. The differential diagnosis of chronic cough in adults and children has its specificities. In certain cases, the etiological factor remains unknown when referring to unexplained (idiopathic) chronic cough. This paper presents the results of a systematic review of publications in medical databases (PubMed) and guidelines from the European Respiratory Society (ERS) and the American College of Chest Physicians (CHEST), related to the diagnosis and treatment of chronic cough. Diagnostic investigations should be focused on the most common causes of chronic cough. In adults, these include asthma, chronic obstructive pulmonary disease, bronchiectasis, interstitial lung disease, lung malignancy, non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airway cough syndrome. In children, the most common causes of chronic cough are asthma, protracted bacterial bronchitis, cystic fibrosis, primary ciliary dyskinesia, bronchiectasis, tracheobronchomalacia, pertussis, habitual (psychogenic) cough, and foreign body aspiration. The treatment primarily involves excluding medications that might have chronic cough as an adverse effect. Therapy is directed toward treating the underlying cause of chronic cough. If the cough persists despite treatment (refractory cough) or if it's idiopathic, neuromodulatory medications are employed (opioids, gamma-aminobutyric acid analogs, tricyclic antidepressants). Therapeutic options also include breathing and vocal techniques, superior laryngeal nerve blocks, and vocal cord medialization injections. Drugs directly inhibiting sensory receptors (P2X3, TRPV-1, and NK-1 inhibitors) are currently under clinical trial investigation. The use of validated tests is crucial for assessing therapeutic effectiveness. The etiological factors of chronic cough can have both infectious and non-infectious origins and are not always related to lung diseases. Considering that chronic cough is regarded as a condition of hypersensitivity, when causal treatment does not yield satisfactory results or when dealing with idiopathic chronic cough, therapy is directed towards central or peripheral neuromodulation, as well as techniques involving breathing and vocal production.

Narrative Review of the Mechanisms and Treatment of Cough in Asthma, Cough Variant Asthma, and Non-asthmatic Eosinophilic Bronchitis.

Chronic cough is a debilitating condition affecting 10-12% of the general population and is one of the leading causes for referral to secondary care. Many conditions have been associated with chronic cough, including asthma, gastro-esophageal reflux disease and upper airways cough syndrome. Inflammatory airway conditions including cough variant asthma (CVA) and non-asthmatic eosinophilic bronchitis (NAEB) contribute to a significant proportion of presentations with chronic cough, with differing diagnostic criteria and different responses to commonly used asthma therapy for their respective diagnoses. Mechanistic studies in both animal models and humans have identified increased neuronal sensitivity and subsequent central sensitization. These mechanisms include inflammatory-mediated nociceptor sensitization and alterations of afferent nerve terminal excitability, phenotypic changes in the vagal afferent neurons over time, and central neuroplasticity resulting from increased synaptic signalling from peripheral afferents. The aim of this review is to discuss the mechanisms, neurophysiology, and management approaches currently available for patients presenting with chronic cough with underlying asthma, CVA, and NAEB and to shed a light on areas of further research required to elucidate the mechanisms of cough in this patient population.

Nonasthmatic Eosinophilic Bronchitis and Asthma: Analysis of Biomarkers.

Nonasthmatic Eosinophilic Bronchitis and Asthma: Analysis of Biomarkers.

Eosinophil Progenitors in Patients With Non-Asthmatic Eosinophilic Bronchitis, Eosinophilic Asthma, and Normal Controls.

ObjectiveThis study aims to explore the potential of in situ airway differentiation of eosinophil progenitors (EoPs) and hematopoietic progenitor cells (HPCs) in sputum and peripheral blood from patients with non-asthmatic eosinophilic bronchitis (NAEB), eosinophilic asthma (EA), and healthy controls (HC).MethodsUsing flow cytometry, we enumerated sputum and blood HPCs and EoPs in patients with NAEB (n=15), EA (n=15), and HC (n=14) at baseline. Patients with NAEB and EA were then treated for 1 month with budesonide (200 μg, bid) or budesonide and formoterol (200/6 μg, bid), respectively. HPCs and EoPs in both compartments were re-evaluated.ResultsAt baseline, NAEB and EA both had significantly greater numbers of sputum but not blood HPCs and EoPs (p<0.05) compared to HC. There were no differences between NAEB and EA. After 1 month of inhaled corticosteroid (ICS) treatment, NAEB patients showed a significant improvement in cough symptoms, but the attenuation of sputum HPC and EoP levels was not significant.ConclusionsNAEB patients have increased airway levels of HPCs and EoPs. One-month treatment with ICS did not fully suppress the level of EoPs in NAEB. Controlling in situ airway differentiation of EoPs may control airway eosinophilia and provide long-term resolution of symptoms in NAEB.

Blood eosinophils as a predictor of treatment response in adults with difficult-to-treat chronic cough.

There is lack of evidence on the role of blood eosinophil count (BEC) as a predictor of treatment response in patients with chronic cough. The study aimed to evaluate BEC as a predictor of treatment response in all non-smoking adults with chronic cough and normal chest radiograph referred to cough clinic and in a subgroup of patients with chronic cough due to asthma or non-asthmatic eosinophilic bronchitis (NAEB).This prospective cohort study included 142 consecutive, non-smoking patients referred to our cough centre due to chronic cough. The management of chronic cough was performed according to the current recommendations. At least a 30-mm decrease of 100-mm visual analogue scale in cough severity and a 1.3 points improvement in Leicester Cough Questionnaire were classified as a good therapeutic response.There was a predominance of females (72.5%), median age 57.5 years with long-lasting, severe cough (median cough duration 60 months, severity 55/100 mm). Asthma and NAEB were diagnosed in 47.2% and 4.9% of patients, respectively. After 12–16 weeks of therapy, a good response to chronic cough treatment was found in 31.0% of all patients. A weak positive correlation was demonstrated between reduction in cough severity and BEC (r=0.28, p<0.001). Area under the curve for all patients with chronic cough was 0.62 with the optimal BEC cut-off for prediction of treatment response set at 237 cells·µL−1 and for patients with chronic cough due to asthma/NAEB was 0.68 (95% CI 0.55–0.81) with the cut-off at 150 cells·µL−1.BEC is a poor predictor of treatment response in adults with chronic cough treated in the cough centre.

GASTRIC ADENOCARCINOMA MASQUERADING AS CHRONIC COUGH

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Chronic cough in adults is defined by cough lasting for at least eight weeks in duration. It remains one of the most common symptoms encountered in ambulatory care, largely attributed to Upper Airway Cough Syndrome (UACS), Asthma, Non-asthmatic Eosinophilic Bronchitis (NAEB), or Gastroesophageal Reflux Disease (GERD). Other less common etiologies shouldn't be overlooked, such as those disorders which stimulate cough receptors. These receptors are located throughout the body including the gastrointestinal tract;irritation of any of these can trigger the vagal-mediated afferent limb of the cough reflex arc. We present the case of a patient with gastric cancer with an initial complaint of three months of cough with associated dyspnea. CASE PRESENTATION: A 33-year-old male with a medical history of obstructive sleep apnea, prior tobacco use, and GERD presented with a three month history of dry cough, fatigue, and dyspnea. Previous primary care visits were conducted via telehealth amid the COVID-19 pandemic, where he was empirically treated with therapies for UACS, asthma, and reflux disease without improvement. His physical exam and chest radiograph were unremarkable. Pulmonary function tests were not obtained secondary to profound coughing with forced exhalation maneuvers. On further questioning, he endorsed early satiety, 10-pound weight loss, and a family history of stomach cancer. CT of the chest demonstrated questionable gastric thickening, retroperitoneal lymphadenopathy surrounding the mesenteric root, a nine millimeter lytic lucency along the right periphery of the 11th thoracic vertebral body, and subtle diffuse peripheral tree-in-bud pulmonary opacities. Bronchoscopy with lavage, brushings, and endobronchial biopsies were negative for infection, granulomas, or malignancy. Upper endoscopy revealed a laterally spreading lesion with central ulceration in the gastric cardia, with biopsy consistent with poorly differentiated gastric adenocarcinoma. Stage IV disease was confirmed by retroperitoneal lymph node sampling. DISCUSSION: Gastric cancer represents 1.4% of all new cancer cases annually in the U.S., most frequently in the sixth decade of life in those with multiple risk factors. Our patient presented nearly three decades earlier with a chronic cough which is exceedingly rare. Plausible risk factors for our patient include male sex, Hispanic ethnicity, obesity, prior tobacco use, and familial predisposition. Early symptoms are equivocal but usually include abdominal pain and weight loss. Respiratory symptoms generally portend late-stage metastasis to the lungs or pulmonary embolism, which our patient did not exhibit. CONCLUSIONS: While UACS, Asthma, NAEB, and GERD remain the most conceivable etiologies of chronic cough, fully investigating all red flag symptoms during patient encounters, with consideration of uncommon causes, endure as foundational tenets of chronic cough evaluation. REFERENCE #1: Irwin RS, French CL, Chang AB, Altman KW, CHEST Expert Cough Panel*. Classification of cough as a symptom in adults and management algorithms: chest guideline and expert panel report. Chest. 2018;153(1):196-209. REFERENCE #2: Kou A, Patel JK, Adetula I, Frunzi J. Gastric cancer presenting as persistent pneumonia: an unusual case report. Cureus. Published online March 21, 2021. REFERENCE #3: Polverino M, Polverino F, Fasolino M, Ando F, Alfieri A, De Blasio F. Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip Respir Med. 2012;7(1):5. DISCLOSURES: No relevant relationships by Patrick Kicker, source=Web Response No relevant relationships by Ashley Soler Acevedo, source=Web Response

ATYPICAL CASE OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a multi-organ vasculitis. However, the hallmarks of the disease are eosinophilia, chronic sinusitis, and asthma. Vasculitic organ involvement might be absent early on, making the diagnosis challenging1. We present the case of a patient with atypical presentation and serology for EGPA. CASE PRESENTATION: A 71-year-old male with a history of non-asthmatic eosinophilic bronchitis, chronic sinusitis, and peripheral eosinophilia (peak 936 cells/uL; 17.6%) was admitted to the hospital with dyspnea and rapidly progressive acute hypoxemic respiratory failure requiring transfer to the intensive care unit. He was started on high flow nasal cannula (60LPM; FiO2 90%-100%). Bilateral crackles noted with no pitting edema. Chest CT showed bilateral airspace disease and ground glass opacities. He tested negative twice for SARS-CoV-2. White blood cell count, kidney function, and brain natriuretic peptide were normal. Autoimmune workup was ordered. He was started on empiric broad-spectrum antibiotic, and gently diuresed. As his presentation was suggestive of eosinophilic lung disease, and in light of significant oxygen requirement, the decision was made to hold on bronchoscopy and start solumedrol at 125mg/day. On ICU Day 3, autoimmune workup showed elevated anti-nuclear antibody titer of 1:160 with a speckled pattern, elevated anti-myeloperoxidase (MPO) antibody titer of 49.4 (p-ANCA), and elevated anti-proteinase-3 (anti-PR3) antibody titers of 18.8 (c-ANCA). Infectious workup was negative. The patient was diagnosed with possible EGPA. He was started on cyclophosphamide in addition to steroids. Oxygen requirement continued to improve. He was discharged home on oxygen at 4LPM and oral steroid with a plan for monthly cyclophosphamide infusion. Follow-up in 2 months with repeat chest CT showed marked improvement. DISCUSSION: The manifestations of EGPA are dynamic, with a few manifestations presenting earlier than others2. With the temporal spacing of signs and symptoms, it is often diagnosed late when more clues are evident. In 1990, the American College of Rheumatology (ACR) established a set of 6 criteria: asthma, peripheral eosinophilia >10%, mononeuropathy or polyneuropathy, migratory pulmonary infiltrates, paranasal sinus abnormality, and biopsy containing blood vessel with extravascular eosinophils2. At least 4 out of six of these criteria must be met to have a diagnosis of EGPA with a specificity of 99.7%. p-ANCA (anti-MPO) is present in around 70% of patients with active EGPA, whereas c-ANCA (anti-PR3) is nearly absent3. Our patient met 3 out of the 6 criteria, and his serology was atypical, showing high titers for both p-ANCA and c-ANCA. CONCLUSIONS: EGPA diagnosis in our patient was not a robust one. However, establishing a presumed diagnosis early and starting immunosuppressive therapy likely saved his life. REFERENCE #1: Guillevin L, Cohen P, Gayraud M, et al. Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore) 1999; 78:26. REFERENCE #2: Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094. REFERENCE #3: Sablé-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005; 143:632 DISCLOSURES: No relevant relationships by Tony Abdo, source=Web Response No relevant relationships by Ahel El Haj Chehade, source=Web Response No relevant relationships by Ahmad Hassan, source=Web Response

Narrative Review: how long should patients with cough variant asthma or non-asthmatic eosinophilic bronchitis be treated?

The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, and approximately 30% to 50% of people with chronic cough have eosinophilic airway inflammation, the presence of which can be confirmed by sputum eosinophilia or elevated exhaled nitric-oxide levels. Cough variant asthma (CVA) is a phenotype of asthma which lacks wheezing or dyspnea, and consistently one of the most common causes of chronic cough worldwide. CVA and non-asthmatic eosinophilic bronchitis (NAEB) shares common feature such as chronic dry cough, eosinophilic inflammation, and development of chronic airflow obstruction (CAO) and asthma in a subset of patients. The distinctive characteristic of these conditions is the presence of airway hyperresponsiveness in CVA but not in NAEB. Coughing is responsive to bronchodilators such as beta-agonists in CVA, but such feature has not been clarified in NAEB. Inhaled corticosteroids (ICSs) are the first-line treatment, and leukotriene receptor antagonists are also effective, in patients with both CVA and NAEB. This review will give an outline of clinical and physiological features, and prognosis and its determinants of CVA and EBNA. Further, the rationale and evidence, despite limited, for the need of long-term treatment will be discussed. The development of airway remodeling due to mechanical stress to the airways exerted by long-standing coughing will also be discussed.

Cough from an allergological as well as from the ENT aspect

Cough from an allergological as well as from the ENT aspect Abstract. Cough is a common problem in the allergological, but less so in the rhinological consultation. The differential diagnostic spectrum for cough is extensive and may range from rhinitis and asthma to eosinophilic esophagitis and rarer diseases. In the case of chronic cough (> 2 months), the four most frequent causes must be sought, or be excluded (upper airway cough syndrome, asthma [cough-variant-asthma], non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease). Aeroallergens such as pollen, house-dust mites or occupational substances play a major role in allergies. Nevertheless, it is not uncommon for cough to be a main symptom of an antibody deficiency or a Sicca symptom complex. The more chronic the cough, the more thoroughly an investigation is indicated - often interdisciplinary. Therapy depends on the cause of the cough. In allergic respiratory diseases, allergy-specific immunotherapy may be indicated.

Should computed tomography and bronchoscopy be routine examinations for chronic cough?

Chronic cough is a common symptom of many diseases. Guidelines on cough from different countries recommend chest X-ray as the first-line examination. However, as compared to computerized tomography (CT), chest X-ray is insensitive in the diagnosis of many diseases. We speculate that CT is more helpful in excluding the causes of long-term cough, such as bronchial tumors and pulmonary interstitial diseases, which prevents patients from receiving unnecessary examinations and diagnostic treatments for chronic cough. In addition, a single chest CT is safe and affordable in some regions. Therefore, chest CT may be recommended as a first-line examination for patients with chronic cough. In addition, although bronchoscopy is employed as a further examination for chronic cough, it plays an important role in the diagnosis of chronic cough, especially in rare bronchial diseases such as amyloidosis and foreign body inhalation. Induced sputum cytology was not accepted as a necessary examination for chronic cough, but it becomes a first-line examination until physicians recognize that non-asthmatic eosinophilic bronchitis is a common cause of chronic cough. Therefore, we speculate that the roles of chest CT and bronchoscopy in the identification of causes of chronic cough are increasingly important; in some regions, or for patients suspicious for uncommon causes of chronic cough, CT and bronchoscopy are recommended as first-line examinations.

Investigations and management of chronic cough: a 2020 update from the European Respiratory Society Chronic Cough Task Force.

Chronic cough affects approximately 10% of the general population, is highest amongst people aged 50 to 60 years, and is twice as common in women than men. It is described to last 8 weeks or longer in adults and does not respond well to treatment with over-the-counter medications and those targeting potential associated conditions. This is a debilitating condition with physical, social, and psychological consequences. The purpose of this review was to highlight the key messages on the management of chronic cough from the task force commissioned by the European Respiratory Society. The assessment of patients with chronic cough should include a thorough detailed history and examination to identify potential causes. The impact and severity can be assessed in a clinic using questionnaires. Potential causes of the condition vary and include, for example, angiotensin‑converting enzyme inhibitors, smoking, asthma, nonasthmatic eosinophilic bronchitis, gastroesophageal reflux disease, and upper airways cough syndrome. In many patients, coughing is persistent despite optimum medical therapy of the underlying medical condition and is hence referred to as refractory chronic cough. In some cases, no cause can be found and the cough is classified as unexplained chronic cough. If treatment of any underlying disease is unsuccessful at controlling cough, then neuromodulatory treatment such as a low‑dose opioid, gabapentin, pregabalin or speech and language therapy may be considered. There is no licensed treatment for chronic cough, but a new class of treatment targeting the purinergic P2X3 receptor is currently in phase 2 and 3 of development.

Elevated Circulating CD4+CD25+CD127-/low Regulatory T Cells in Patients with Non-asthmatic Eosinophilic Bronchitis.

Non-asthmatic eosinophilic bronchitis (NAEB) is a common cause of chronic cough. It is characterized by sputum eosinophilia like asthma but lacks airway hyperresponsiveness. Regulatory T cells (Tregs) are recognized as immune suppressors and are involved in the pathogenesis of asthma. However, the relationship between Tregs and NAEB remains unknown. This study aimed to preliminarily explore the role of Tregs in NAEB by comparing circulating Tregs levels to asthma and healthy controls. Fractional exhaled nitric oxide (FeNO), spirometry with bronchial provocation test, sputum induction and blood routine test were performed in all subjects. Peripheral blood mononuclear cells were used to detect the Tregs (CD4+CD25+CD127-/low) by flow cytometry. Relationship between the levels of circulating Tregs and clinical indexes was also observed. A total of 15 patients with NAEB, 20 patients with asthma and 11 healthy controls were included. The absolute numbers of circulating Tregs in the NAEB group (49.8 ± 18.9 × 103 cells/ml) and asthma group (53.3 ± 18.7 × 103 cells/ml) were higher than that in healthy control group (32.7 ± 11.6 × 103 cells/ml) (both P < 0.01). In total, the level of circulating Tregs showed positive correlation with FeNO (r = 0.30, P < 0.05). Tregs may play a key role not only in asthmatic patients, but also in patients with NAEB, as reflected by the elevated Tregs in peripheral blood.

Current Status and Future Directions of Chronic Cough in China.

Chronic cough is one of the most common complaints for which patients in China seek medical attention. However, there are no nationwide data on the prevalence and socioeconomic burden of chronic cough. Although approximately 50% of Chinese men smoke, the vast majority of patients presenting for evaluation of chronic cough are never smokers. An equal sex distribution and a middle-aged predominance have been observed in the Chinese chronic cough population, despite demonstration of a higher cough reflex sensitivity in females and older patients. The role of air pollution in the distinct age and sex distribution requires further study. In terms of the etiologies of chronic cough in China, cough-variant asthma, upper airway cough syndrome, nonasthmatic eosinophilic bronchitis, and atopic cough are the most common causes, comprising 75.2% to 87.6% of cases across different regions. Chinese Guidelines for Diagnosis and Treatment of Cough were initially published in 2005, and updated in 2009 and 2016. In addition, the China Cough Coalition was established in 2016. Great progress has been made in both cough-related clinical practice and research in recent years, however, there are still challenges ahead. To facilitate optimal management of chronic cough in China, efforts promoting the dissemination and application of published guidelines will be essential, especially in community-based healthcare and in rural regions. As chronic refractory cough has been identified as a huge challenge to clinicians worldwide, continued international cooperation will be essential in optimizing evaluation and management of chronic cough.

Fibrocyte localisation to the ASM bundle in asthma: bidirectional effects on cell phenotype and behaviour.

ObjectivesAirway hyper‐responsiveness and persistent airflow obstruction contribute to asthma pathogenesis and symptoms, due in part to airway smooth muscle (ASM) hypercontractility and increased ASM mass. Fibrocytes have been shown to localise to the ASM in asthma however it is not known whether fibrocytes localise to the ASM in nonasthmatic eosinophilic bronchitis (NAEB) and chronic obstructive pulmonary disease (COPD). In addition, the potential consequences of fibrocyte localisation to ASM as regards asthma pathophysiology has not been widely studied.MethodsFibrocytes and proliferating cells were enumerated in ASM in bronchial tissue using immunohistochemistry. The effects of primary ASM and fibrocytes upon each other in terms of phenotype and behaviour following co‐culture were investigated by assessing cell number, size, apoptotic status, phenotype and contractility in in vitro cell‐based assays.ResultsIncreased fibrocyte number in the ASM was observed in asthma versus NAEB, but not NAEB and COPD versus controls, and confirmed in asthma versus controls. ASM proliferation was not detectably different in asthmatics versus healthy controls in vivo. No difference in proliferation, apoptotic status or size of ASM was seen following culture with/without fibrocytes. Following co‐culture with ASM from asthmatics versus nonasthmatics, fibrocyte smooth muscle marker expression and collagen gel contraction were greater. Following co‐culture, fibrocyte CD14 expression was restored with the potential to contribute to asthma pathogenesis via monocyte‐mediated processes dependent on the inflammatory milieu.ConclusionFurther understanding of mechanisms of fibrocyte recruitment to and/or differentiation within the ASM may identify novel therapeutic targets to modulate ASM dysfunction in asthma.

Optimising the use of polar symptoms in Homoeopathy: Introduction to a pilot study of prognostic factor research in chronic cough

Background: Polar symptoms represent the most challenging rubrics in the homoeopathic repertories, despite their frequent use. Objective: The study objective was to assess the relationship between 27 polar cough symptoms, 3 non-polar cough symptoms and 30 general polar symptoms and successful response to specific homoeopathic medicines. Materials and Methods: A multi-centre, explorative, prospective, observational study was conducted at ten centres under the Central Council for Research in Homoeopathy. Two hundred and sixteen patients were enrolled with chronic cough, lasting >8 weeks. The patients were enrolled as per four underlying diagnoses of chronic upper airway cough syndrome (CUACS), gastro-oesophageal reflux disease (GERD), asthma and related syndromes, and non-asthmatic eosinophilic bronchitis (NAEB). 30 general polar symptoms, 27 polar cough symptoms and 3 non-polar cough symptoms were assessed at the baseline. During enrollment and follow-up consultations, two validated questionnaires (Leicester Cough Questionnaire chronic and EuroQuol (EQ)-5D-5L) were filled for assessing the effect of treatment. If the Physician Assessment Score was >2, the causal relationship between improvement and prescribed medicine was further assessed using Modified Naranjo Algorithm. Results: At the fourth follow-up, three medicines with >10 cases having good result were identified: Phosphorus (n = 20), Pulsatilla (n = 19) and Sulphur (n = 13). For this introductory article, we compare some results with the existing data, reflect on discrepancies between the existing data and research outcome and reflect on future use, especially in respiratory tract infections (RTIs). Conclusion: In improving the homoeopathic method and its practical use, priority should be given to polar symptoms, especially related to RTIs.