Assessing the effect of transcranial magnetic stimulation on peak cough flow in patients with supratentorial cerebral infarction: A retrospective cohort study.

Respiratory dysfunction following supratentorial cerebral infarction leads to pneumonia and is a major cause of mortality. Decreased voluntary cough function impairs the ability to clear mucus or secretions from the airways and increases the risk of aspiration pneumonia. Peak cough flow (PCF) is one of the objective tools for evaluating voluntary cough function. Repetitive transcranial magnetic stimulation (rTMS) could be applied to the respiratory motor cortex to improve respiratory function. Little is known about the effect of rTMS on PCF in patients with supratentorial cerebral infarction during the subacute period. This study aimed to determine whether rTMS treatment could improve PCF in patients with supratentorial cerebral infarction. We retrospectively recruited patients with subacute supratentorial cerebral infarction who underwent a PCF test. The rTMS group received a combination of rTMS treatment for 2 weeks and conventional rehabilitation for 4 weeks. However, the control group underwent only conventional rehabilitation for 4 weeks. PCF tests were performed before and after treatment and the results were compared between the 2 groups. In total, 145 patients with supratentorial cerebral infarctions were recruited. The PCF parameters before and after treatment increased in both the rTMS and control groups. However, the rTMS group showed a greater increase in PCF values compared with the control group. In patients with supratentorial cerebral infarction, the combination of conventional rehabilitation and rTMS in the subacute period may be helpful in improving voluntary cough function compared with conventional rehabilitation alone.

A 21-Year-Old Man With Dyspnea, Wheezing, and Cough.

CASE PRESENTATION: A 21-year-old male college student presented for a second opinion with low alpha-1 antitrypsin (AAT) levels and complaints of episodic dyspnea with wheezing and cough. He was a never smoker with a medical history of frequent respiratory tract infections in early childhood and allergy to dander, dust mites, peanuts, and eggs. There was no travel history outside of the continental United States. His mother had asthma. His symptoms were not controlled on inhaled corticosteroids and bronchodilators. His AAT genotype was found to be PI∗SZ, and augmentation therapy (with pooled human-plasma derived AAT) was recommended locally.

The role of neuronal excitation and inhibition in the pre-Bötzinger complex on the cough reflex in the cat.

Brainstem respiratory neuronal network significantly contributes to cough motor pattern generation. Neuronal populations in the pre-Bötzinger complex (PreBötC) represent a substantial component for respiratory rhythmogenesis. We studied the role of PreBötC neuronal excitation and inhibition on mechanically induced tracheobronchial cough in 15 spontaneously breathing, pentobarbital anesthetized adult cats (35 mg/kg, iv initially). Neuronal excitation by unilateral microinjection of glutamate analog d,l-homocysteic acid resulted in mild reduction of cough abdominal electromyogram (EMG) amplitudes and very limited temporal changes of cough compared with effects on breathing (very high respiratory rate, high amplitude inspiratory bursts with a short inspiratory phase, and tonic inspiratory motor component). Mean arterial blood pressure temporarily decreased. Blocking glutamate-related neuronal excitation by bilateral microinjections of nonspecific glutamate receptor antagonist kynurenic acid reduced cough inspiratory and expiratory EMG amplitude and shortened most cough temporal characteristics similarly to breathing temporal characteristics. Respiratory rate decreased and blood pressure temporarily increased. Limiting active neuronal inhibition by unilateral and bilateral microinjections of GABAA receptor antagonist gabazine resulted in lower cough number, reduced expiratory cough efforts, and prolongation of cough temporal features and breathing phases (with lower respiratory rate). The PreBötC is important for cough motor pattern generation. Excitatory glutamatergic neurotransmission in the PreBötC is involved in control of cough intensity and patterning. GABAA receptor-related inhibition in the PreBötC strongly affects breathing and coughing phase durations in the same manner, as well as cough expiratory efforts. In conclusion, differences in effects on cough and breathing are consistent with separate control of these behaviors.NEW & NOTEWORTHY This study is the first to explore the role of the inspiratory rhythm and pattern generator, the pre-Bötzinger complex (PreBötC), in cough motor pattern formation. In the PreBötC, excitatory glutamatergic neurotransmission affects cough intensity and patterning but not rhythm, and GABAA receptor-related inhibition affects coughing and breathing phase durations similarly to each other. Our data show that the PreBötC is important for cough motor pattern generation, but cough rhythmogenesis appears to be controlled elsewhere.

Influence of intrathoracic vagotomy on the cough reflex in the anesthetized cat.

Recurrent laryngeal afferent fibers are primarily responsible for cough in response to mechanical or chemical stimulation of the upper trachea and larynx in the guinea pig. Lower airway slowly adapting receptors have been proposed to have a permissive effect on the cough reflex. We hypothesized that vagotomy below the recurrent laryngeal nerve branch would depress mechanically or chemically induced cough. In anesthetized, bilaterally thoracotomized, artificially ventilated cats, thoracic vagotomy nearly eliminated cough induced by mechanical stimulation of the intrathoracic airway, significantly depressed mechanically stimulated laryngeal cough, and eliminated capsaicin-induced cough. These results support an important role of lower airway sensory feedback in the production of tracheobronchial and laryngeal cough in the cat. Further, at least some of this feedback is due to excitation from pulmonary volume-sensitive sensory receptors.

Respiratory Characteristics in Patients With Major Burn Injury and Smoke Inhalation.

This study aimed to evaluate pulmonary function measurements and respiratory muscle parameters in patients with major burn injury and smoke inhalation. The inclusion criteria included patients who were diagnosed with a smoke inhalation burn or a major burn of more than 20% of total body surface area (TBSA). All subjects underwent a pulmonary function test, respiratory muscle strength test, peak cough flow and fluoroscopic diaphragmatic movement measurement, and 6-minute walk test before starting pulmonary rehabilitation. Evaluations were conducted on the 88th day after the injury, the average time of admission to the Department of the Rehabilitation Medicine for burn rehabilitation after the completion of the acute treatment. The average degree of burns of the total 67 patients was 34.6% TBSA. All parameters in the patient group were significantly lower than the healthy controls, and a mild restrictive pattern of impairment with a reduction in diffusing capacity and more reduced expiratory muscle, than inspiratory muscle strength were observed. Peak cough flow, respiratory muscle strength, and forced vital capacity in the patient group with inhalation burn were significantly lower than in those without inhalation burn. The conditions of the majority of patients with major burn and inhalation injury were consistent with restrictive impairment and significant reduction in diffusion capacity. The patients had expiratory muscle weakness, decreased diaphragmatic movement, and exercise capacity impairment.

Vedolizumab-associated pulmonary manifestations in children with ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: The off-label use of vedolizumab (VDZ) for inflammatory bowel disease in children is increasing. We report on possibly the first case of VDZ-associated pulmonary manifestations in paediatrics. CASE SUMMARY: This report details the case of a 13-year-old child with ulcerative colitis who was initiated on VDZ due to persistent active disease. After the first three doses, he developed a persistent and productive cough. Microbiological work-up was normal. VDZ discontinuation led to the resolution of symptoms. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case report of VDZ-associated pulmonary manifestations in paediatrics. A direct, pro-inflammatory effect of VDZ has been hypothesized, but further studies are warranted.

Description of Epidemiological Features, Symptoms and Mortality of the Patients with COVID-19 in Some Provinces of Iran.

BACKGROUND: Clinical manifestations of COVID-19 are different. There are some risk factors for COVID-19. This study aimed to describe the epidemiological features, symptoms and mortality of the patients with COVID-19 in Iran. METHODS: This were a cohort study performed on 103,179 patients with COVID-19. The demographic and clinical data were collected in selected provinces. The required data of all patients was extracted from the COVID registry system and analyzed using STATA version 14 and Excel 2016. RESULTS: The mean age was 52.40 years for men and 52.41 years for women. About 55.2% of the study population were male and 44.8% were female. Totally, 60.9% (5085) of deaths happened in men and 39.1% (3263) in women. The mean time from onset of symptoms to hospitalization in men and women were 3.47 and 3.48 days, respectively. The mean time from onset of symptoms to isolation was 2.81 days in men and was 2.87 days in women, from onset of symptoms to death was 9.29 and 9.54 days, respectively, from onset of symptoms to discharge was 7.47 and 7.39 days, and from hospitalization to death was 6.76 and 7.05 days. Cough and shortness of breath were the most common symptoms in the patients. CONCLUSION: According to the results, the overall mortality rate was higher in men than women. Women with cardiovascular disease and diabetes were more likely to die. The mean time from onset of symptoms to hospitalization, isolation, and discharge was similar in men and women.

Prostaglandin E2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 channels.

BACKGROUND: Cough hypersensitivity is a major characteristic feature associated with several types of cough, including chronic cough, but its underlying mechanisms remain to be fully understood. Inflammatory mediators, such as prostaglandin E2 (PGE2), have been implicated in both peripheral induction and sensitization of the cough reflex. In this study, using a conscious guinea pig model of cough, we investigated whether PGE2 can sensitize the cough reflex via central actions and, if so, via which mechanisms. METHODS: All drugs were administered by intracerebroventricular (i.c.v.) route and whole-body plethysmograph set-up was used for both induction, using aerosolized citric acid (0.2 M), and recording of cough. Immunohistochemistry was performed to confirm the expression of NaV 1.8 channels in the nucleus tractus solitarius (nTS). RESULTS: We show that both PGE2 and the non-selective EP1/EP3 agonist, sulprostone, dose-dependently enhanced the citric acid-induced cough (P ≤ 0.001, P ≤ 0.01, respectively). Pretreatment with the EP1 antagonist, ONO-8130, did not affect the sulprostone-induced cough sensitization, whilst the EP3 antagonist, L-798,106, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, treatment with either the EP2 agonist, butaprost or the EP4 agonist, L-902,688, had no effect on cough sensitization. Additionally, pretreatment with either the TRPV1 antagonist, JNJ-17203212 or the TRPA1 antagonist, HC-030031, alone or in combination, nor with the NaV 1.1, 1.2, 1.3, 1.4, 1.6 and 1.7 channel blocker, tetrodotoxin, had any effect on the cough. In contrast, pretreatment with the NaV 1.8 antagonist, A-803467, dose-dependently inhibited this effect (P ≤ 0.05). Furthermore, NaV 1.8 channels were shown to be expressed in the nTS. CONCLUSION: Collectively, our findings show that PGE2 sensitizes the cough reflex centrally via EP3 receptor-dependent activation of NaV 1.8 but independently of TRPV1,TRPA1 and TTX-sensitive sodium channel activation. These results indicate that PGE2 plays an important role in central sensitization of the cough reflex and suggest that central EP3 receptors and/or NaVv 1.8 channels may represent novel antitussive molecular targets.

A 30-Year-Old Immune Deficient Woman With Persistent Cough and Shortness of Breath.

CASE PRESENTATION: A 30-year-old woman was referred with increasing shortness of breath and cough in the setting of GATA2 deficiency. She initially presented 9 years previously with recurrent episodes of pneumonia and sinusitis. Genetic testing revealed a heterozygous GATA2 mutation (c.988C>T). She has since had multiple infections that have included necrotizing fasciitis of the right thumb, recurrent pilonidal infections (which required 23 procedures), esophageal candidiasis, and human papillomavirus-positive high-grade squamous intraepithelial lesion of the cervix. Serial bone marrow biopsy specimens showed persistent hypocellularity (20% to 60%) with intermittent erythroid atypia and variable detection of trisomy 8, which were concerning for evolving myelodysplastic syndrome. One year before the current admission, she was diagnosed with disseminated Mycobacterium avium complex and was treated with rifabutin, ethambutol, and azithromycin. She was taking voriconazole, acyclovir, and trimethoprim-sulfamethoxazole prophylaxis.

A 70-Year-Old Man With Cough and Recurrent Respiratory Infections.

CASE PRESENTATION: A 70-year-old man was referred for evaluation of recurrent respiratory infections requiring antibiotics and chronic cough over 3 years. Two months prior to presentation, he started to develop blood-tinged sputum but not frank hemoptysis. He otherwise denied any fever, chills, night sweats, or weight loss. He had dyspnea during the respiratory infections but not otherwise. His medical history was significant for chronic rhinitis without sinusitis and a low serum IgM level. He was a never smoker and a farmer but otherwise had no significant or specific exposures or travel history. His family history was significant for alpha-1 antitrypsin deficiency in his mother.

A 51-Year-Old Man With a Large Posterior Mediastinal Mass.

CASE PRESENTATION: A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

Predictive power of extubation failure diagnosed by cough strength: a systematic review and meta-analysis.

BACKGROUND: The predictive power of extubation failure diagnosed by cough strength varies by study. Here we summarise the diagnostic power of extubation failure tested by cough strength. METHODS: A comprehensive online search was performed to select potentially eligible studies that evaluated the predictive power of extubation failure tested by cough strength. A manual search was also performed to identify additional studies. Data were extracted to calculate the pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) to evaluate the predictive power of extubation failure. RESULTS: A total of 34 studies involving 45 study arms were enrolled, and 7329 patients involving 8684 tests were analysed. In all, 23 study arms involving 3018 tests measured cough peak flow before extubation. The pooled extubation failure was 36.2% and 6.3% in patients with weak and strong cough assessed by cough peak flow, respectively. The pooled sensitivity, specificity, positive LR, negative LR, DOR, and AUC were 0.76 (95% confidence interval [CI]: 0.72-0.80), 0.75 (0.69-0.81), 2.89 (2.36-3.54), 0.37 (0.30-0.45), 8.91 (5.96-13.32), and 0.79 (0.75-0.82), respectively. Moreover, 22 study arms involving 5666 tests measured the semiquantitative cough strength score (SCSS) before extubation. The pooled extubation failure was 37.1% and 11.3%, respectively, in patients with weak and strong cough assessed by the SCSS. The pooled sensitivity, specificity, positive LR, negative LR, DOR, and AUC were 0.53 (95% CI: 0.41-0.64), 0.83 (0.74-0.89), 2.50 (1.93-3.25), 0.65 (0.56-0.76), 4.61 (3.03-7.01), and 0.74 (0.70-0.78), respectively. CONCLUSIONS: Weak cough is associated with increased extubation failure. Cough peak flow is superior to the SCSS for predicting extubation failure. However, both show moderate power for predicting extubation failure.

Identifying individuals with recent COVID-19 through voice classification using deep learning.

Recently deep learning has attained a breakthrough in model accuracy for the classification of images due mainly to convolutional neural networks. In the present study, we attempted to investigate the presence of subclinical voice feature alteration in COVID-19 patients after the recent resolution of disease using deep learning. The study was a prospective study of 76 post COVID-19 patients and 40 healthy individuals. The diagnoses of post COVID-19 patients were based on more than the eighth week after onset of symptoms. Voice samples of an 'ah' sound, coughing sound and a polysyllabic sentence were collected and preprocessed to log-mel spectrogram. Transfer learning using the VGG19 pre-trained convolutional neural network was performed with all voice samples. The performance of the model using the polysyllabic sentence yielded the highest classification performance of all models. The coughing sound produced the lowest classification performance while the ability of the monosyllabic 'ah' sound to predict the recent COVID-19 fell between the other two vocalizations. The model using the polysyllabic sentence achieved 85% accuracy, 89% sensitivity, and 77% specificity. In conclusion, deep learning is able to detect the subtle change in voice features of COVID-19 patients after recent resolution of the disease.

Abnormal FeV1 and body mass index are associated with impaired cough-related quality of life in sarcoidosis patients.

Sarcoidosis is a granulomatous disease that mainly manifests within the lungs and may thereby impair lung function. Beyond and independently from organ impairment, sarcoidosis may affect quality of life which can be quantified by questionnaires. The Leicester Cough Questionnaire (LCQ) has been developed to assess cough-related quality of life. We analysed data from a prospectively collected cohort of sarcoidosis patients for validation of the German LCQ version. Our analyses demonstrated that LCQ values add additional information beyond routinely monitored parameters (e.g. lung function). Only FeV1 and BMI slightly influence LCQ scores, where all other parameters tested did not correlate with LCQ scores. In summary, LCQ is a valuable tool providing information on the patient' quality of life beyond routine follow-up parameters. FeV1 and BMI may represent treatable traits to reduce cough-related disease burden.

Management of functional communication, swallowing, cough and related disorders: consensus recommendations for speech and language therapy.

Communication problems (eg, dysphonia, dysfluency and language and articulation disorders), swallowing disorders (dysphagia and globus), cough and upper airway symptoms, resulting from functional neurological disorder (FND), are commonly encountered by speech and language professionals. However, there are few descriptions in the literature of the most effective practical management approaches. This consensus document aims to provide recommendations for assessment and intervention that are relevant to both adults and young people. An international panel of speech and language professionals with expertise in FND were approached to take part. Participants responded individually by email to a set of key questions regarding best practice for assessment and interventions. Next, a video conference was held in which participants discussed and debated the answers to these key questions, aiming to achieve consensus on each issue. Drafts of the collated consensus recommendations were circulated until consensus was achieved. FND should be diagnosed on the basis of positive clinical features. Speech and language therapy for FND should address illness beliefs, self-directed attention and abnormal movement patterns through a process of education, symptomatic treatment and cognitive behavioural therapy within a supportive therapeutic environment. We provide specific examples of these strategies for different symptoms. Speech and language professionals have a key role in the management of people with communication and related symptoms of FND. It is intended that these expert recommendations serve as both a practical toolkit and a starting point for further research into evidence-based treatments.

Clinical relevance of SARS-CoV-2 infection in late pregnancy.

BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.

Modeling the survival times of the COVID-19 patients with a new statistical model: A case study from China.

Over the past few months, the spread of the current COVID-19 epidemic has caused tremendous damage worldwide, and unstable many countries economically. Detailed scientific analysis of this event is currently underway to come. However, it is very important to have the right facts and figures to take all possible actions that are needed to avoid COVID-19. In the practice and application of big data sciences, it is always of interest to provide the best description of the data under consideration. The recent studies have shown the potential of statistical distributions in modeling data in applied sciences, especially in medical science. In this article, we continue to carry this area of research, and introduce a new statistical model called the arcsine modified Weibull distribution. The proposed model is introduced using the modified Weibull distribution with the arcsine-X approach which is based on the trigonometric strategy. The maximum likelihood estimators of the parameters of the new model are obtained and the performance these estimators are assessed by conducting a Monte Carlo simulation study. Finally, the effectiveness and utility of the arcsine modified Weibull distribution are demonstrated by modeling COVID-19 patients data. The data set represents the survival times of fifty-three patients taken from a hospital in China. The practical application shows that the proposed model out-classed the competitive models and can be chosen as a good candidate distribution for modeling COVID-19, and other related data sets.

Differential effects of acute cerebellectomy on cough in spontaneously breathing cats.

The role of the cerebellum in controlling the cough motor pattern is not well understood. We hypothesized that cerebellectomy would disinhibit motor drive to respiratory muscles during cough. Cough was induced by mechanical stimulation of the tracheobronchial airways in anesthetized, spontaneously breathing adult cats (8 male, 1 female), and electromyograms (EMGs) were recorded from upper airway, chest wall, and abdominal respiratory muscles. Cough trials were performed before and at two time points after total cerebellectomy (10 minutes and >1 hour). Unlike a prior report in paralyzed, decerebrated, and artificially ventilated animals, we observed that cerebellectomy had no effect on cough frequency. After cerebellectomy, thoracic inspiratory muscle EMG magnitudes increased during cough (diaphragm EMG increased by 14% at 10 minutes, p = 0.04; parasternal by 34% at 10 minutes and by 32% at >1 hour, p = 0.001 and 0.03 respectively). During cough at 10 minutes after cerebellectomy, inspiratory esophageal pressure was increased by 44% (p = 0.004), thyroarytenoid (laryngeal adductor) muscle EMG amplitude increased 13% (p = 0.04), and no change was observed in the posterior cricoarytenoid (laryngeal abductor) EMG. Cough phase durations did not change. Blood pressure and heart rate were reduced after cerebellectomy, and respiratory rate also decreased due to an increase in duration of the expiratory phase of breathing. Changes in cough-related EMG magnitudes of respiratory muscles suggest that the cerebellum exerts inhibitory control of cough motor drive, but not cough number or phase timing in response to mechanical stimuli in this model early after cerebellectomy. However, results varied widely at >1 hour after cerebellectomy, with some animals exhibiting enhancement or suppression of one or more components of the cough motor behavior. These results suggest that, while the cerebellum and behavior-related sensory feedback regulate cough, it may be difficult to predict the nature of the modulation based on total cerebellectomy.

Managing Cough in Idiopathic Pulmonary Fibrosis.

In many studies, more than one-half of patients with idiopathic pulmonary fibrosis (IPF) endorse cough. In IPF (as in other conditions), when chronic, cough may be frustrating and lead to significant impairments in quality of life. In patients with IPF, comorbid conditions such as gastroesophageal reflux can cause or contribute to cough; when stemming from IPF itself, chronic cough likely arises from multiple mechanisms including mechanical and neurosensory changes. In this article, we review our approach at attempting to identify causes of chronic cough in patients with IPF; these include gastroesophageal reflux disease or upper airway cough syndrome and IPF itself. We cursorily summarize the current evidence for the treatment of chronic cough in IPF, briefly review data on the treatment of unexplained chronic cough and extrapolate it to the treatment of refractory cough in IPF, but we focus our attention on our approaches to evaluation and management, recognizing that some may not be supported by a robust cache of data.