SLeuthing Tuberculous Cough.

Cough, a hallmark of tuberculosis, transmits the disease. Ruhl et al. find that a Mycobacterium tuberculosis (Mtb)-specific lipid, SL-1, stimulates human nociceptive neurons and makes guinea pigs cough. Mtb extract, but not SL-1, also stimulates non-nociceptive neurons that participate in the cough reflex, suggesting additional cough-inducing mechanisms.

Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.

Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.

Infectious and Inflammatory Pathways to Cough.

Coughing is a dynamic physiological process resulting from input of vagal sensory neurons innervating the airways and perceived airway irritation. Although cough serves to protect and clear the airways, it can also be exploited by respiratory pathogens to facilitate disease transmission. Microbial components or infection-induced inflammatory mediators can directly interact with sensory nerve receptors to induce a cough response. Analysis of cough-generated aerosols and transmission studies have further demonstrated how infectious disease is spread through coughing. This review summarizes the neurophysiology of cough, cough induction by respiratory pathogens and inflammation, and cough-mediated disease transmission.

Herb-CMap: a multimodal fusion framework for deciphering the mechanisms of action in traditional Chinese medicine using Suhuang antitussive capsule as a case study.

Herbal medicines, particularly traditional Chinese medicines (TCMs), are a rich source of natural products with significant therapeutic potential. However, understanding their mechanisms of action is challenging due to the complexity of their multi-ingredient compositions. We introduced Herb-CMap, a multimodal fusion framework leveraging protein-protein interactions and herb-perturbed gene expression signatures. Utilizing a network-based heat diffusion algorithm, Herb-CMap creates a connectivity map linking herb perturbations to their therapeutic targets, thereby facilitating the prioritization of active ingredients. As a case study, we applied Herb-CMap to Suhuang antitussive capsule (Suhuang), a TCM formula used for treating cough variant asthma (CVA). Using in vivo rat models, our analysis established the transcriptomic signatures of Suhuang and identified its key compounds, such as quercetin and luteolin, and their target genes, including IL17A, PIK3CB, PIK3CD, AKT1, and TNF. These drug-target interactions inhibit the IL-17 signaling pathway and deactivate PI3K, AKT, and NF-κB, effectively reducing lung inflammation and alleviating CVA. The study demonstrates the efficacy of Herb-CMap in elucidating the molecular mechanisms of herbal medicines, offering valuable insights for advancing drug discovery in TCM.

Respiratory disease in rhesus macaques inoculated with SARS-CoV-2.

An outbreak of coronavirus disease 2019 (COVID-19), which is caused by a novel coronavirus (named SARS-CoV-2) and has a case fatality rate of approximately 2%, started in Wuhan (China) in December 20191,2. Following an unprecedented global spread3, the World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although data on COVID-19 in humans are emerging at a steady pace, some aspects of the pathogenesis of SARS-CoV-2 can be studied in detail only in animal models, in which repeated sampling and tissue collection is possible. Here we show that SARS-CoV-2 causes a respiratory disease in rhesus macaques that lasts between 8 and 16 days. Pulmonary infiltrates, which are a hallmark of COVID-19 in humans, were visible in lung radiographs. We detected high viral loads in swabs from the nose and throat of all of the macaques, as well as in bronchoalveolar lavages; in one macaque, we observed prolonged rectal shedding. Together, the rhesus macaque recapitulates the moderate disease that has been observed in the majority of human cases of COVID-19. The establishment of the rhesus macaque as a model of COVID-19 will increase our understanding of the pathogenesis of this disease, and aid in the development and testing of medical countermeasures.

DAT, deacylating autotransporter toxin, from Bordetella parapertussis demyristoylates Gαi GTPases and contributes to cough.

The pathogenic bacteria Bordetella pertussis and Bordetella parapertussis cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We previously reported that pertussis toxin (PTx), which inactivates heterotrimeric GTPases of the Gi family through ADP-ribosylation of their α subunits, causes coughing in combination with Vag8 and lipid A in B. pertussis infection. In contrast, the mechanism of cough induced by B. parapertussis, which produces Vag8 and lipopolysaccharide (LPS) containing lipid A, but not PTx, remained to be elucidated. Here, we show that a toxin we named deacylating autotransporter toxin (DAT) of B. parapertussis inactivates heterotrimeric Gi GTPases through demyristoylation of their α subunits and contributes to cough production along with Vag8 and LPS. These results indicate that DAT plays a role in B. parapertussis infection in place of PTx.

Emergency department visits respond nonlinearly to wildfire smoke.

Air pollution negatively affects a range of health outcomes. Wildfire smoke is an increasingly important contributor to air pollution, yet wildfire smoke events are highly salient and could induce behavioral responses that alter health impacts. We combine geolocated data covering all emergency department (ED) visits to nonfederal hospitals in California from 2006 to 2017 with spatially resolved estimates of daily wildfire smoke PM[Formula: see text] concentrations and quantify how smoke events affect ED visits. Total ED visits respond nonlinearly to smoke concentrations. Relative to a day with no smoke, total visits increase by 1 to 1.5% in the week following low or moderate smoke days but decline by 6 to 9% following extreme smoke days. Reductions persist for at least a month. Declines at extreme levels are driven by diagnoses not thought to be acutely impacted by pollution, including accidental injuries and several nonurgent symptoms, and declines come disproportionately from less-insured populations. In contrast, health outcomes with the strongest physiological link to short-term air pollution increase dramatically in the week following an extreme smoke day: We estimate that ED visits for asthma, COPD, and cough all increase by 30 to 110%. Data from internet searches, vehicle traffic sensors, and park visits indicate behavioral changes on high smoke days consistent with declines in healthcare utilization. Because low and moderate smoke days vastly outweigh high smoke days, we estimate that smoke was responsible for an average of 3,010 (95% CI: 1,760-4,380) additional ED visits per year 2006 to 2017. Given the increasing intensity of wildfire smoke events, behavioral mediation is likely to play a growing role in determining total smoke impacts.

Validated Clinical Score to Predict Gastroesophageal Reflux in Patients With Chronic Laryngeal Symptoms: COuGH RefluX.

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict the likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms. METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms who underwent objective testing (upper gastrointestinal endoscopy and/or ambulatory reflux monitoring) between March 2018 and May 2023. The training phase identified a model with optimal receiver operating characteristic curves, and ß coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model. RESULTS: A total of 856 adults, 304 in the training cohort and 552 in the validation cohort, were included. In the training phase, the optimal predictive model (area under the curve, 0.68; 95% CI, 0.62-0.74), was the Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX (COuGH RefluX) score, with a lower threshold of 2.5 and an upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an area under the curve of 0.67 (95% CI, 0.62-0.71), with 79% sensitivity and 81% specificity for proven GERD. CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict the likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

Case 323: Minute Pulmonary Meningothelial-like Nodules.

HISTORY: A 70-year-old woman with a 6-year history of asthma, a 12-year history of diabetes mellitus, and who did not smoke presented to the pulmonology clinic with dyspnea and cough. Chest CT performed 5 years earlier for similar symptoms revealed multiple pulmonary nodules. However, she was lost to follow-up before the work-up was concluded. Otherwise, her medical history was unremarkable. Family history included maternal endometrial cancer. Physical examination revealed partial oxygen saturation of 98%, respiratory rate of 18 breaths per minute, and heart rate of 77 beats per minute. Her breath sounds and other systemic findings were normal. Pulmonary function test results were as follows: forced expiratory volume in 1 second, 108% predicted (normal range, 80%-120%); total lung capacity, 72% predicted (normal range, 80%-120%); forced vital capacity, 101% predicted (normal range, 80%-120%); diffusing capacity for carbon monoxide, 69% predicted (normal range, 60%-120%); and forced midexpiratory flow, 85% predicted (normal range, 40%-160%). Complete blood count, erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor, and antinuclear antibody levels were within normal limits. The patient underwent volumetric thin-section CT of the chest using a multidetector CT scanner (Ingenuity Core 128; Philips Medical Systems) to evaluate lung nodules and pulmonary interstitium.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis.

BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS: In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT. CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.

Identifying vagal bronchopulmonary afferents mediating cough response to inhaled sulfur dioxide in mice.

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1-2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1-3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2.NEW & NOTEWORTHY This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Comparison Results of Three-Port Robot-Assisted and Uniportal Video-Assisted Lobectomy for Functional Recovery Index in the Treatment of Early Stage Non-small Cell Lung Cancer: A Propensity Score-Matched Analysis.

BACKGROUND: Minimally invasive lobectomy is the standard treatment for early stage non-small cell lung cancer (NSCLC). The aim of this study is to investigate postoperative recovery in a prospective trial of discharged patients with early stage non-small cell lung cancer undergoing robot-assisted thoracic surgery (RATS) versus uniportal video-assisted thoracic surgery (UVATS). PATIENTS AND METHODS: This is a prospective and observational study. From 9 September 2022 to 1 July 2023, 178 patients diagnosed with NSCLC admitted to the Department of Thoracic Surgery of Shandong Provincial Hospital signed informed consent and underwent lobectomy by RATS and UVATS. The functional recovery index included MD Anderson Symptom Inventory, Christensen Fatigue Scale, EORTC QLQ-C30, and Leicester Cough Questionnaire. RESULTS: After propensity score-matched analysis, each group included 42 cases. For the baseline characteristics of patients, operation time (p = 0.01) and length of stay (p = 0.04) were shorter in the RATS group. The number of lymph nodes resected in the RATS group was much more than in the UVATS group. According to our investigation, appetite loss, nausea, diarrhea, and cough severity after RATS were better than after UVATS. After the first week, pain severity degree of the RATS group was higher than UVATS, while there was no difference during the second and third week. The physical score of the RATS group was higher than the UVATS group (p = 0.04), according to the Leicester Cough Questionnaire. CONCLUSION: RATS was associated with severe short-term postoperative pain but less postoperative complications.

Cough flows as a criterion for decannulation of autonomously breathing patients with tracheostomy tubes.

BACKGROUND: Adequate cough or exsufflation flow can indicate an option for safe tracheostomy decannulation to noninvasive management. Cough peak flow via the upper airways with the tube capped is an outcome predictor for decannulation readiness in patients with neuromuscular impairment. However, this threshold value is typically measured with tracheotomy tube removed, which is not acceptable culturally in China. The aim of this study was to assess the feasibility and safety of using cough flow measured with tracheostomy tube and speaking valve (CFSV) > 100 L/min as a cutoff value for decannulation. STUDY DESIGN: Prospective observational study conducted between January 2019 and September 2022 in a tertiary rehabilitation hospital. METHODS: Patients with prolonged tracheostomy tube placement were referred for screening. Each patient was assessed using a standardized tracheostomy decannulation protocol, in which CFSV greater than 100 L/min indicated that the patients' cough ability was sufficient for decannulation. Patients whose CFSV matched the threshold value and other protocol criteria were decannulated, and the reintubation and mortality rates were followed-up for 6 months. RESULTS: A total of 218 patients were screened and 193 patients were included. A total of 105 patients underwent decannulation, 103 patients were decannulated successfully, and 2 patients decannulated failure, required reinsertion of the tracheostomy tube within 48 h (failure rate 1.9%). Three patients required reinsertion or translaryngeal intubation within 6 months. CONCLUSIONS: CFSV greater than 100 L/min could be a reliable threshold value for successful decannulation in patients with various primary diseases with a tracheostomy tube. TRIAL REGISTRATION: This observational study was not registered online.

The burden of cough in idiopathic pulmonary fibrosis and other interstitial lung diseases: a systematic evidence synthesis.

BACKGROUND: Cough remains a persistent symptom in patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). To inform future research, treatment and care models, we conducted the first systematic synthesis of evidence on its associated burden. METHODS: A literature search was performed for articles published between January 2010 and October 2023 using databases including Embase, MEDLINE and the Cochrane Library. Studies in patients with IPF and other ILDs reporting cough-related measures were eligible for inclusion. Included studies were categorised based on the types of ILD they examined and their design. Study details, patient characteristics and outcomes were extracted, and the risk of bias was assessed. A narrative synthesis approach was employed to interpret the findings. RESULTS: Sixty-one studies were included: 33 in IPF, 18 in mixed-ILDs, six in connective tissue disease-associated-ILDs and four in sarcoidosis. Across the studies, a range of tools to assess cough and its impact were used. The most frequently used measures of cough were cough severity visual analogue scale (VAS) and objective cough counts, whereas the most frequently used health-related quality of life (HRQoL)/impact measures were the St. George's Respiratory Questionnaire (SGRQ) and Leicester Cough Questionnaire (LCQ). In IPF, studies consistently reported correlations between various cough and HRQoL measures, including between cough VAS scores and objective cough counts, LCQ scores and SGRQ scores. Similar correlations were observed in studies in other ILDs, but data were more limited. Qualitative studies in both IPF and other ILDs consistently highlighted the significant cough-related burden experienced by patients, including disruption of daily activities, fatigue and social embarrassment. Although there were no studies specifically investigating the economic burden of cough, one study in patients with fibrotic ILD found cough severity was associated with workplace productivity loss. CONCLUSIONS: Our study underscores the heterogeneity in assessing cough and its impact in IPF and other ILDs. The findings confirm the negative impact of cough on HRQoL in IPF and suggest a comparable impact in other ILDs. Our synthesis highlights the need for standardised assessment tools, along with dedicated studies, particularly in non-IPF ILDs and on the economic burden of cough.

Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study.

BACKGROUND AND OBJECTIVE: To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). METHODS: A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. RESULTS: After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). CONCLUSION: DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. TRIAL REGISTRATION: The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) [ChiCTR2200056246].

Antibiotics Not Associated with Shorter Duration or Reduced Severity of Acute Lower Respiratory Tract Infection.

BACKGROUND: Antibiotic use remains common for the treatment of lower respiratory tract infections. The objective of this study was to evaluate the impact of antibiotic use on the duration and severity of acute lower respiratory tract infection (LRTI). PARTICIPANTS: Adult patients presenting to US primary or urgent care sites with a chief complaint of cough and symptoms consistent with LRTI. MAIN MEASURES: Collected data included demographics, comorbidities, symptoms, and 48 viral and bacterial respiratory pathogens by PCR. Severity of signs/symptoms was reported for up to 28 days using diaries and text messages. Interpolation was used where data were missing. KEY RESULTS: Of 718 patients with baseline data, 29% had an antibiotic prescribed at baseline. The most common antibiotics were amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin in 85% of patients. Provision of an antibiotic had no effect on the duration or overall severity of cough, including in patients with viral, bacterial, and mixed infections. Receipt of an antibiotic did reduce the likelihood of a follow-up visit (14.1% vs 8.2%, aOR 0.47, 95% CI 0.26-0.84), perhaps by removing the motivation of getting an antibiotic at a follow-up visit. However, they were also more likely to receive a systemic corticosteroid (31.9% vs 4.5%, p < 0.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, p < 0.001). Patients believed that receiving an antibiotic would reduce the duration of their illness by nearly 4 days. CONCLUSIONS: In this large prospective study in the US primary and urgent care setting, antibiotics had no measurable impact on the severity or duration of cough due to acute LRTI. Patients had unrealistic expectations regarding the duration of LRTI and the effect of antibiotics which should be the target of antibiotic stewardship efforts.

Clinical correlates of respiratory disorders in patients with severe multiple sclerosis: A cross-sectional cohort.

BACKGROUND: Respiratory disorders remain incompletely described in multiple sclerosis (MS), even though they are a frequent cause of death. METHODS: The objective was to describe respiratory disorders in MS patients with Expanded Disability Status Score (EDSS) ⩾ 6.5. Diaphragm dysfunction was defined by at least two of the seven criteria: clinical signs, inspiratory recruitment of neck muscles during wakefulness, reduced upright vital capacity (VC) < 80%, upright-to-supine VC ⩾ 15% of upright VC, decrease in Maximal Inspiratory Pressure < 60%, phasic activation of inspiratory neck muscles during sleep, and opposition of thoracic and abdominal movements during sleep. Cough weakness was defined by a peak cough flow < 270 L/min and/or need for cough assist. Sleep apnea syndrome was defined by an apnea-hypopnea index ⩾ 15. RESULTS: Notably, 71 MS patients were included: median age 54 [48, 61] years; median disease duration 21.4 [16.0, 31.4] years. Of these, 52 patients had one or more respiratory disorders; diaphragm dysfunction was the most frequent (n = 34). Patients with diaphragm dysfunction and cough weakness were more disabled. The fatigue score and the cognitive evaluations did not differ between the groups. Five patients required non-invasive ventilation. CONCLUSION: Respiratory disorders are frequent in severe MS, mostly diaphragm dysfunction. Of interest, instrumental interventions are available to address these disorders.