Effects of respiratory muscle training on cough function in neurological disorders: A systematic review with meta-analysis.

BACKGROUND: Patients with neurological disorders can present the weakness of respiratory muscle and impaired cough function. Previous studies have shown that respiratory muscle strength training (RMT) is an effective method of improving the strength of respiratory muscle. The effects of RMT on cough function remain controversial. OBJECTIVE: We aimed to analyze randomized controlled trials (RCTs) that investigated the effects of RMT on cough function of patients with neurological disorders. METHODS: Pubmed, Medline, Embase, and the Cochrane Library were searched electronically for RCTs. Two reviewers independently performed data extraction and quality assessment. Data were analyzed by using RevMan 5.3 software of The Cochrane Collaboration. RESULTS: Five studies with 185 participants were included. The mean PEDro score was 6.2 (range 5 to 7), showing moderate methodological quality. Random-effects meta-analyses showed that respiratory muscle training improved peak expiratory cough flow of voluntary cough by 2.16 (95% CI 1.16 to 3.17) and involuntary cough by 2.84 (95% CI 1.29 to 4.39), with statistical significance (P < 0.0001, P = 0.0003). The experimental group had an improvement of 0.19 cmH2O (95% CI -0.12 to 0.5) on the maximal inspiratory pressure, 0.09 cmH2O (95% CI -0.23 to 0.42) on the maximal expiratory pressure, but with no statistical significance (P = 0.23, P = 0.58) between groups. CONCLUSION: Respiratory muscle training was considered as an effective method for improving cough function. However, this review was insufficient to conclude whether respiratory muscle training was effective in improving inspiratory and expiratory muscle strength, this was opposite with previous meta-analysis. These effects might due to the small samples and different diseases.

Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Epidemiology and clinical characteristics of 43 COVID-19 patients in Weifang, China.

BACKGROUND: To investigate the epidemiology and clinical characteristics of patients infected with coronavirus disease 2019 (COVID-19) in Weifang, China. METHODS: The demographic data of 43 COVID-19 patients identified in Weifang were used to investigate whether they had traveled to epidemic areas and whether they had close contact with confirmed cases. On admission, patients' symptoms and results of laboratory tests and imaging were analyzed. RESULTS: Among the 43 COVID-19 patients. including 9 third generation infected cases, 16 (37.2%) were imported, who infected the rest. Most cases were middle-aged with approximate sex ratio. A "super spreader", Mr. Zhang made it necessary to quarantine 69 medical personnel. Mr. Zhang directly infected six individuals who, in turn, infected another six individuals. Another patient, Mr. Wang, spread the infection to his five family members at a family gathering. Subsequently, the daughter infected her husband. The most common COVID-19 symptoms were fever, weakness, dry cough, and cough sputum. In most patients, white blood cell counts were not elevated and lymphocyte counts were decreased. Elevated C-reactive protein and serum amyloid A protein (SAA) levels were commonly observed. There was no death among the patients or infection among the medical staff. CONCLUSIONS: The infection by the COVID-19 in Weifang was mostly the result of close contact with imported cases. These circumstances underscore the need to comprehensively strengthen the management for patients to prevent and control the spread of the virus.

Modified rehabilitation exercises for mild cases of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by a new Betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a global pandemic. Gathered clinicopathological evidence in COVID-19 patients shows that alveoli injuries and interstitial changes are the major mechanisms of impaired O2/CO2 exchange. Few rehabilitation exercises concerning COVID-19 patients were reported. Here, we present a modified version of rehabilitation exercises based on the underlying mechanism of the disease to mild cases of COVID-19. These exercises aimed to improve the pulmonary function of patients and ease the expectoration process. Additionally, an essential branch of Traditional Chinese Medicine (TCM) named acupressure was integrated into the exercises to facilitate the recovery and maintenance of pulmonary function. METHODS: From March 4, 2020 to May 5, 2020, a total of 60 COVID-19 patients who completed the full course of MRE were enrolled in this observational study. The diagnostic and classification criteria were based on the 7th edition of Diagnosis and Treatment Guideline of COVID-19 published by the National Health Commission of the People's Republic of China. We prospectively gathered patients' reported outcomes concerning respiration-related symptoms at four different time points, including: (I) at admission; (II) at the time of hospital discharge; (III) two weeks after discharge; (IV) four weeks after discharge. The reported respiratory symptoms included dry cough, productive cough, difficulty in expectoration, and dyspnea. RESULTS: In total, 60 confirmed mild COVID-19 cases were enrolled with a median age of 54 years old. The baseline prevalence for dry cough, productive cough, difficulty in expectoration, and dyspnea were 41.7%, 43.3%, 35.0%, and 50.0%, respectively. The pronounced decline in symptom prevalence was recorded over time. Interestingly, four weeks after discharge, we noticed a lower remission rate in productive cough and difficulty in expectoration. CONCLUSIONS: The modified rehabilitation exercises were retrieved from the Eight-Section Brocade, and are specifically designed for rehabilitation of COVID-19 patients at home or health facilities. Based on current findings on pronouncedly improved remission rate in respiratory symptoms, we recommend the MRE as suitable rehabilitation exercise to smooth respiration and ease the expectoration process in mild COVID-19 cases.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

The chemical profile of active fraction of Kalimeris indica and its quantitative analysis.

Kalimeris indica (L) Sch-Bip is a medicinal plant used by the Miao ethnic group in the Guizhou province of China. It is widely used as a fresh vegetable to treat colds, diarrhea and gastric ulcers. However, few studies have been conducted on the mechanism of its effect on colds, and its quality control. The anticomplement and antitussive activities of different polar extracts of K. indica were evaluated. Fifty-nine compounds, mainly including phenols and flavonoids, were identified in K. indica extract by ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. A method was established through ultra-high-performance liquid chromatography with a photodiode array to simultaneously determine the anticomplement and antitussive activity of five compounds in K. indica combining chemical identification with chemometrics for discrimination and quality assessment. Also, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid exhibited significantly higher anticomplementary activity than the other three compounds. The quantitative data were further analyzed by principal component analysis and orthogonal partial least-squares discriminant analysis. Heatmap visualization was conducted to clarify the distribution of the major compounds in different geographical origins. Screening pharmacological activities by a combination of chemometrics and chemical identification might be an effective method for the quality control of K. indica.

Effectiveness of expiratory muscle strength training on expiratory strength, pulmonary function and cough in the adult population: a systematic review.

BACKGROUND: Respiratory muscle strength declines in certain disease states, leading to impaired cough, reduced airway clearance and an increased risk of aspiration pneumonia. Respiratory muscle training may therefore reduce this risk. OBJECTIVES: To assess current evidence of expiratory muscle strength training (EMST) on maximum expiratory pressure, cough flow and spirometry. DATA SOURCES: Databases including CINAHL, Medline, Science Direct and PEDRo were searched. ELIGIBILITY CRITERIA: Randomised controlled trials investigating expiratory muscle strength training on maximum expiratory pressure, pulmonary function or cough in any adult population, published before December 2017. STUDY APPRAISAL: Data were extracted to a trial description form and study quality evaluated by two reviewers. Meta-analysis was performed with calculation of mean differences and 95% confidence intervals. RESULTS: Nine studies met inclusion criteria and ranged in size from 12 to 42 participants. Trials investigated EMST in healthy adults (2), multiple sclerosis (3), COPD (2), acute stroke (1) and spinal cord injury (1). Overall, EMST improved maximum expiratory pressure (15.95cmH2O; 95% CI: 7.77 to 24.12; P<0.01) with no significant impact on cough flow (4.63L/minute; 95%CI -27.48 to 36.74; P=0.78), forced vital capacity (-0.16L; 95%CI -0.35 to 0.02; P=0.09) or forced expiratory volume in 1second (-0.09L; 95%CI -0.10 to -0.08; P<0.001) vs control or sham training. CONCLUSIONS: Meta-analysis indicated a small significant increase in maximum expiratory pressure following EMST. Improvements in maximum expiratory pressure did not lead to improvements in cough or pulmonary function. LIMITATIONS: Variations in protocol design and population limited the overall effect size. Systematic Review Registration PROSPERO CRD42018104190.

Anticomplement and antitussive activities of major compound extracted from Chimonanthus nitens Oliv. leaf.

Chimonanthus nitens Oliv. leaf (CNOL), as a traditional Chinese medicine, has been widely used for the treatment of influenza and colds over a long history. However, the mechanism of colds related to the effects of CNOL have been little studied. In this study, the anticomplement and antitussive activities of different polarity extracts of CNOL were evaluated. Ethyl acetate extract (EAE) among different extracts not only significantly decreased cough times by 21-58% (P < 0.01), but also had anticomplement effects demonstrated by the CH50 values of 0.100 mg/ml. A total of 28 constituents (10 coumarins, 13 flavonoids and five phenolics) were identified in EAE based on the ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry technique. Eight compounds in EAE were evaluated by an ammonia-induced cough model to reveal the antitussive mechanisms and classical anticomplement pathway. The results indicated that the antitussive effects of scopoletin, kaempferol-3-O-rutinoside and kaempferol may depend on central mechanisms and that flavonoids such as compounds of kaempferol-3-O-rutinoside and kaempferol have better anticomplementary activity than coumarins like compounds of scopolin, scopoletin and isofraxidin. Taken together, kaempferol-3-O-rutinoside and kaempferol could be important chemical markers in the present study that might be used to evaluate the quality and biological activity of CNOL.

Response to bronchodilator and clinical, pathophysiological features in patients with nonasthmatic eosinophilic bronchitis.

INTRODUCTION: Whether nonasthmatic eosinophilic bronchitis (NAEB) shows response to bronchodilator (RB) remains unclear. OBJECTIVES: To investigate the RB and its relationship with clinical and pathophysiological features in NAEB. METHODS: Fifty-one patients with NAEB were assigned in a 2:1 ratio to receive oral bambuterol hydrochloride (n = 34, 10 mg, once daily, for 3 days) or matched placebo (n = 17) randomly, of whom 48 patients (32 with bronchodilator and 16 with placebo) completed the study. Sputum induction, spirometry and cough reflex sensitivity were measured. RB was considered when cough Visual analogue scale (VAS) score decreased 30% or more after treatment. Cough reflex sensitivity was defined as the lowest concentration of capsaicin inducing five coughings or more (C5), and presented as Log C5. RESULTS: The responsive rate of patients with bronchodilator was significantly higher than that with placebo (34.4% vs 6.3%, P < 0.05). The VAS score decreased significantly in patients with bronchodilator (median: 6.0-3.0, P < 0.01). There was a significantly higher median Log C5 (2.7 vs 1.3, P < 0.05), and a higher trend of decline in FEV1 % predicted and MMEF% predicted after bronchial provocation in patients with RB as compared with patients without RB. No significant differences in baseline percentages of sputum eosinophil were found between patients with RB and that without RB. CONCLUSIONS: One third of patients with NAEB respond well to bronchodilator treatment, which are related with lower cough reflex sensitivity and increased airway responsiveness. The relationship between NAEB and asthma needs to be investigated further.

Cervical Interferential Current Transcutaneous Electrical Sensory Stimulation for Patients with Dysphagia and Dementia in Nursing Homes.

PURPOSE: We aimed to determine the efficacy of interferential current transcutaneous electrical sensory stimulation (IFC-TESS) in patients with dementia who were being treated for dysphagia in nursing homes under normal living conditions. PATIENTS AND METHODS: This study recruited 54 nursing home residents (13 males, 41 females; mean age, 84.5 ± 10.7 years) with dysphagia and dementia. IFC-TESS was performed with Gentle Stim® (Careido Co. Ltd., Kanagawa, Japan) for 15 minutes. Two sessions per day were administered 5 days per week, for 3 weeks. The outcomes included the improvement of the patients' cough reflexes and nutritional states across the 3 weeks of intervention; the former was evaluated with the cough test based on the changes in cough latency time and cough frequency, while the latter was assessed based on changes in the functional oral intake scale (FOIS) score and oral calorie intake. RESULTS: The cough latency times before and after the 3-week intervention were 15.8 (7.0-60.0) and 6.7 (3.6-30.7) s/min, respectively; the cough frequencies were 5.0 (0.0-5.0) and 5.0 (5.0-5.0) t/min, respectively; the FOIS scores were 5.0 (5.0-6.0) and 5.0 (5.0-6.0), respectively; and oral calorie intakes were 1300.0 (862.5-1420.0) and 1300.0 (1005.0-1462.5) kcal/day, respectively. All parameters significantly improved across the intervention (p < 0.05). When the results were adjusted for age, sex, body mass index, mini nutritional assessment results, Barthel index, and mini-mental state examination scores, IFC-TESS improved the cough reflex and oral calorie intake in older nursing home residents with dementia. CONCLUSION: Cervical IFC-TESS can improve the cough reflexes and nutritional states of patients with dysphagia and dementia in nursing homes. As it has previously been difficult to perform active rehabilitation with dementia patients, IFC-TESS may be effective and practicable for the rehabilitation of this patient population.

Eficacia de la miel para el tratamiento de la tos aguda en niños atendidos en forma ambulatoria / Efficacy of honey for treatment of acute cough in pediatric outpatients

A partir de una consulta en la central de emergencias de un niño con tos aguda, el autor del artículo realiza una búsqueda bibliográfica para revisar la evidencia sobre el uso de la miel para aliviar este síntoma. Luego de la lectura crítica de una revisión sistemática, el autor concluye que ésta podría ser una alternativa elegible frente a los jarabes para la tos, por su perfil de seguridad y su posible beneficio en el alivio de la tos. (AU)

Based on a consultation at the emergency room of a child with acute cough, the author of this article performs a bibliographic search to review the evidence on the use of honey to alleviate this symptom. After the critical appraisal of a systematic review, the author concludes that honey could be an eligible alternative to cough syrups, due to its safety profile and its possible benefit in cough relief. (AU)

DT-0111: a novel drug-candidate for the treatment of COPD and chronic cough.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) plays important mechanistic roles in pulmonary disorders in general and chronic obstructive pulmonary disease (COPD) and cough in particular. The effects of ATP in the lungs are mediated to a large extent by P2X2/3 receptors (P2X2/3R) localized on vagal sensory nerve terminals (both C and Aδ fibers). The activation of these receptors by ATP triggers a pulmonary-pulmonary central reflex, which results in bronchoconstriction and cough, and is also proinflammatory due to the release of neuropeptides from these nerve terminals via the axon reflex. These actions of ATP in the lungs constitute a strong rationale for the development of a new class of drugs targeting P2X2/3R. DT-0111 is a novel, small, water-soluble molecule that acts as an antagonist at P2X2/3R sites. METHODS: Experiments using receptor-binding functional assays, rat nodose ganglionic cells, perfused innervated guinea pig lung preparation ex vivo, and anesthetized and conscious guinea pigs in vivo were performed. RESULTS: DT-0111 acted as a selective and effective antagonist at P2X2/3R, that is, it did not activate or block P2YR; markedly inhibited the activation by ATP of nodose pulmonary vagal afferents in vitro; and, given as an aerosol, inhibited aerosolized ATP-induced bronchoconstriction and cough in vivo. CONCLUSIONS: These results indicate that DT-0111 is an attractive drug-candidate for the treatment of COPD and chronic cough, both of which still constitute major unmet clinical needs. The reviews of this paper are available via the supplementary material section.

Abdominal Functional Electrical Stimulation to Augment Respiratory Function in Spinal Cord Injury.

Background: Functional electrical stimulation (FES) is the application of electrical pulses to a nerve to achieve a functional muscle contraction. Surface electrical stimulation of the nerves that innervate the abdominal muscles, termed abdominal FES, can cause the abdominal muscles to contract, even when paralysed after spinal cord injury. As the abdominal muscles are the major expiratory muscles, and commonly partially or completely paralysed in tetraplegia, abdominal FES offers a promising method of improving respiratory function for this patient group. Objective: The aim of the article is to provide readers with a better understanding of how abdominal FES can be used to improve the health of the spinal cord-injured population. Methods: A narrative review of the abdominal FES literature was performed. Results: Abdominal FES can achieve an immediate effective cough in patients with tetraplegia, while the repeated application over 6 weeks of abdominal FES can improve unassisted respiratory function. Ventilator duration and tracheostomy cannulation time can also be reduced with repeated abdominal FES. Conclusion: Abdominal FES is a noninvasive method to achieve functional improvements in cough and respiratory function in acute and chronically injured people with tetraplegia. Potential practical outcomes of this include reduced ventilation duration, assisted tracheostomy decannulation, and a reduction in respiratory complications. All of these outcomes can contribute to reduced morbidity and mortality, improved quality of life, and significant potential cost savings for local health care providers.

Do clinical investigations predict long-term wheeze? A follow-up of pediatric respiratory outpatients.

INTRODUCTION: The contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear. AIM: We performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma. METHODS: We studied children aged 6 to 16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnea, or cough in 2007. The initial assessment included spirometry, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up 7 years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression. RESULTS: At baseline, 111 children were examined in 2007. After 7 years, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio, 4.2; 95% CI, 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence. CONCLUSION: Reported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.

Non-pharmacological interventions for chronic cough: The past, present and future.

Non-pharmacological interventions have been explored in people with refractory chronic cough. Normally delivered by Physiotherapists and or Speech and Language Therapists, these interventions aim to educate patients about their cough, provide them with cough suppression techniques and breathing exercises, improve vocal/laryngeal hydration and psychoeducational counselling to help them gain greater control of their cough. Six key studies have been completed over the past 12 years that have consistently found non-pharmacological interventions help to improve quality of life and reduce cough frequency. Some studies also found improvements in cough reflex sensitivity and severity. Despite promising results there now needs to be further work to optimise these interventions. There is a need to standardise terminology used such as relabelling the intervention as cough control therapy and move away from uni-disciplinary terms. Standardised patient selection, including screening protocols, optimal timing and delivery of the interventions as well as the outcome measures used to evaluate interventions need further exploration.

Indicaciones y seguimiento domiciliario de la tos asistida mecánica en el paciente neuromuscular / Indications and domiciliary follow-up of mechanical insufflation-exsufflation in patients with neuromuscular disorders

Introducción: La insuflación-exuflación mecánica (MI-E) es una importante terapia respiratoria para el enfermo neuromuscular, pero existen pocos datos publicados en relación con su uso en el domicilio. Objetivo: Evaluar las características clínicas de los pacientes en los que se prescribe la MI-E y analizar su cumplimiento, seguridad y causas de retirada a largo plazo. Material y métodos: Estudio observacional retrospectivo de 78 adultos con enfermedad neuromuscular a los que se les prescribió MI-E a domicilio en un hospital de tercer nivel entre enero de 2009 y junio de 2015. Se describen las características clínicas y funcionales en el momento de la indicación de la terapia, la frecuencia y los parámetros de uso, los efectos secundarios, así como las causas de abandono de la terapia y la mortalidad. Resultados: La mayoría de los pacientes eran hombres (67%), con una mediana de edad de 58 años. El diagnóstico mayoritario fue la esclerosis lateral amiotrófica (45% de los casos). Tenían afectación bulbar moderada-grave el 36% y el 22% utilizaba el dispositivo solo en fase insuflatoria. El 14% de los pacientes eran portadores de traqueostomía y el 69% de los casos utilizaban también ventilación mecánica. El cuidador era mayoritariamente quien realizaba la técnica (86%), diariamente en el 73% de los casos. Desde la prescripción fallecieron el 38% de los pacientes, la mayoría afectados de esclerosis lateral amiotrófica (96%), con una mediana de supervivencia de 8 meses. En un 6% la MI-E se retiró por ineficacia. Se describió un solo caso de efecto secundario, que no contraindicó el uso de la terapia. Conclusiones: La MI-E prescrita a domicilio es una técnica segura, con cumplimiento adecuado, incluso en pacientes con afectación bulbar y asociada a ventilación mecánica. Se constata la dependencia del enfermo hacia su cuidador para su práctica

Introduction: Mechanical insufflation-exsufflation (MI-E) is an important respiratory therapy for neuromuscular disorders, but there are few published data on its use at home. Objective: To assess the clinical characteristics of patients prescribed MI-E, and to analyse compliance, safety, and causes for long-term withdrawal. Material and methods: Retrospective observational study of 78 adults with neuromuscular disorders who were prescribed MI-E at home in a third level hospital from January 2009 to June 2015. The clinical and functional characteristics when the therapy was indicated, the frequency and parameters of use, adverse effects and causes of withdrawal and mortality were evaluated. Results: Most patients were men (67%) with a median age of 58 years. The main diagnosis was amyotrophic lateral sclerosis (45% of cases). Moderate-severe bulbar involvement was present in 36%, and 22% used the device only in the insufflation phase. Fourteen percent of patients had a tracheostomy and 69% of the patients underwent mechanical ventilation. MI-E was mostly performed by the caregiver (86%), on a daily basis in 73% of the patients. After prescription, 38% patients died; most of these patients had amyotrophic lateral sclerosis (96%), with a median survival of 8 months. In 6%, MI-E was withdrawn due to ineffectiveness. An adverse effect was reported in only one patient and did not contraindicate the use of the therapy. Conclusions: In our experience, MI-E prescribed at home was well tolerated and safe, even in patients with bulbar involvement. Patients showed good compliance with MI-E alone or associated with mechanical ventilation, but required help from caregivers for its performance

Isolation of novel biflavonoids from Cardiocrinum giganteum seeds and characterization of their antitussive activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Cardiocrinum giganteum var. yunnanense (Leichtlin ex Elwes) Stearn (Liliaceae), also known as Doulingzi, have been used as a folk substitute for conventional antitussive herb "Madouling" (Aristolochia species) to treat chronic bronchitis and pertussis. The active antitussive phytochemicals in C. giganteum seeds are not known. AIM OF THE STUDY: The present work aims at isolating the active phytochemicals in C. giganteum seeds and confirming their antitussive effects. MATERIALS AND METHODS: Active chemicals were isolated from C. giganteum seeds ethanol extract and identified their structures. Antitussive effects were evaluated with the cough frequency of guinea pigs exposed to citric acid. Electrical stimulation of the superior laryngeal nerve in guinea pigs was performed to differentiate the acting site of potential antitussives. RESULTS: Two racemic biflavonoids (CGY-1 and CGY-2) were isolated from C. giganteum seeds. CGY-1 was identified as (S)-2″R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone-7- methyl ether, which are new compounds and firstly isolated from C. giganteum seeds. Racemic CGY-2 was identified as (S)-2″R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone. Both CGY-1 and CGY-2 could significantly inhibit coughs induced by inhalation of citric acid. Further, they acted on the peripheral reflex pathway to inhibit cough after electrical stimulation of the superior laryngeal nerve in guinea pigs. CONCLUSIONS: These chemicals isolated from C. giganteum seeds showed good antitussive effects. The data provide scientific evidence to support the traditional use of C. giganteum seeds as an antitussive herbal medicine.

The effects of respiratory muscle training on peak cough flow in patients with Parkinson's disease: a randomized controlled study.

OBJECTIVE: To compare the effects of an inspiratory versus and expiratory muscle-training program on voluntary and reflex peak cough flow in patients with Parkinson disease. DESIGN: A randomized controlled study. SETTING: Home-based training program. PARTICIPANTS: In all, 40 participants with diagnosis of Parkinson's disease were initially recruited in the study and randomly allocated to three study groups. Of them, 31 participants completed the study protocol (control group, n = 10; inspiratory training group, n = 11; and expiratory training group, n = 10) Intervention: The inspiratory and expiratory group performed a home-based inspiratory and expiratory muscle-training program, respectively (five sets of five repetitions). Both groups trained six times a week for two months using a progressively increased resistance. The control group performed expiratory muscle training using the same protocol and a fixed resistance. MAIN MEASURES: Spirometric indices, maximum inspiratory pressure, maximum expiratory pressure, and peak cough flow during voluntary and reflex cough were assessed before and at two months after training. RESULTS: The magnitude of increase in maximum expiratory pressure ( d = 1.40) and voluntary peak cough flow ( d = 0.89) was greater for the expiratory muscle-training group in comparison to the control group. Reflex peak cough flow had a moderate effect ( d = 0.27) in the expiratory group in comparison to the control group. Slow vital capacity ( d = 0.13) and forced vital capacity ( d = 0.02) had trivial effects in the expiratory versus the control group. CONCLUSIONS: Two months of expiratory muscle-training program was more beneficial than inspiratory muscle-training program for improving maximum expiratory pressure and voluntary peak cough flow in patients with Parkinson's disease.

Impulse oscillometry measurement of distal airways obstruction in depleted uranium-exposed Gulf War veterans.

INTRODUCTION: A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium-related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens. METHODS: We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values. RESULTS: Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%). CONCLUSIONS: While oscillometry identified more veterans as obstructed, obstruction was not uranium-related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

The research of the possible mechanism and the treatment for capsaicin-induced cough.

Unexplained chronic cough (UCC) affects millions of patients worldwide. New therapeutic approaches to this condition are urgently needed, since current treatment options provide only symptomatic relief. Cough reflex hypersensitivity has been shown to play an important role in the pathogenesis of UCC. The transient receptor potential vanilloid type 1 (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological treatment of UCC. The aim of this study was to explore the efficacy and the possible mechanism of SB705498, a TRPV1 antagonist, for cough in a capsaicin-induced cough animal model (i.e. guinea pigs). Induction of cough by capsaicin was successfully implemented in the guinea pigs, and the animals that met the inclusion criteria were randomly divided into four treatment groups: (1) Saline inhalation group (NSInh group, N = 10, negative control group), (2) Codeine phosphate intraperitoneal injection group (CPInp group, N = 10, positive control group), (3) SB705498 inhalation group (SBInh group, N = 10), (4) SB705498 intragastric administration group (SBIng group, N = 10). After treatment with above compounds, the capsaicin-induced cough experiment was performed again. The cough numbers and the cough incubation periods were recorded to evaluate the antitussive effect of SB705498. Enzyme-linked immunosorbent assay (ELISA) testing and Immunohistochemistry (IHC) staining for substance P (SP), calcitonin gene related peptide (CGRP) and neurokinin A (NKA) expression in lung and brain tissues were performed as an indication of neurogenic inflammation. Hematoxylin-Eosin (H&E) staining was used to observe the pathology morphology of lung and brain tissues. When the CPInp, SBInh and SBIng groups were compared to the NSInh group, the cough numbers were significantly reduced (p < .001), while the cough incubation periods were significantly prolonged (P < .001). In addition, the expression of SP, CGRP and NKA in lung and brain tissue was reduced (P < .05). None of the animals in the four groups exhibited lung and brain parenchymal inflammation. The results from this study showed that SB705498 had a significant antitussive effect, could reduce the neurogenic inflammation by reducing the expression of SP, CGRP and NKA in a capsaicin-induced cough model of guinea pigs. The results further indicated that TRPV1 played an important role in UCC and SB705498 might be a promising therapeutic agent for UCC.