Weak Cough Research Articles

Computational Modeling of Cough Droplet Behavior in the Human Upper Respiratory Airway

Abstract This study investigated the interaction of cough droplets with airflow in a realistic human airway. The ultimate aim was to understand the behavior of cough droplets inside the airway and to assess the potential of droplets to be retained in the airway or transmitted to the lungs. A computational fluid dynamics (CFD) model, based on the Euler–Lagrangian framework, was employed to predict the two-phase, droplet-laden transient cough flow in a realistic three-dimensional (3D) human airway. The airway geometry was reconstructed from patient computed tomography (CT) scan dataset. The discrete phase model was used to track the motion of the droplets in the air flow. Two distinct cough profiles—a strong cough and a weak cough—acquired experimentally from human subjects, were used as input to simulate normal and disordered cough functions. The effects of cough strength and droplet size on droplet retention and aspiration in the airway were investigated. It was found that droplet retention was significantly higher for a weak cough compared to a strong cough. For a weak cough, the highest droplet retention percentage exceeded 60%, while for a strong cough, it was less than 20%. Larger sized droplets were more likely to be aspirated into the lungs, especially under weak cough conditions. In the case of weak cough, more than 5% of the 200 μm sized droplets were aspirated into the lungs, whereas for strong cough, aspiration was less than 2%.

Evaluation and management of dyspnea as the dominant presenting feature in neuromuscular disorders.

Dyspnea is a common symptom in neuromuscular disorders and, although multifactorial, it is usually due to respiratory muscle involvement, associated musculoskeletal changes such as scoliosis or, in certain neuromuscular conditions, cardiomyopathy. Clinical history can elicit symptoms such as orthopnea, trepopnea, sleep disruption, dysphagia, weak cough, and difficulty with secretion clearance. The examination is essential to assist with the diagnosis of an underlying neurologic disorder and determine whether dyspnea is from a cardiac or pulmonary origin. Specific attention should be given to possible muscle loss, use of accessory muscles of breathing, difficulty with neck flexion/extension, presence of thoraco-abdominal paradox, conversational dyspnea, cardiac examination, and should include a detailed neurological examination directed at the suspected differential diagnosis. Pulmonary function testing including sitting and supine spirometry, measures of inspiratory and expiratory muscle strength, cough peak flow, sniff nasal inspiratory pressure, pulse oximetry, transcutaneous CO2, and arterial blood gases will help determine the extent of the respiratory muscle involvement, assess for hypercapnic or hypoxemic respiratory failure, and qualify the patient for noninvasive ventilation when appropriate. Additional testing includes dynamic imaging with sniff fluoroscopy or diaphragm ultrasound, and diaphragm electromyography. Polysomnography is indicated for sleep related symptoms that are not otherwise explained. Noninvasive ventilation alleviates dyspnea and nocturnal symptoms, improves quality of life, and prolongs survival. Therapy targeted at neuromuscular disorders may help control the disease or favorably modify its course. For patients who have difficulty with secretion clearance, support of expiratory function with mechanical insufflation-exsufflation, oscillatory devices can reduce the aspiration risk.

Upper Airway and Translaryngeal Resistance During Mechanical Insufflation-Exsufflation

Mechanical insufflation-exsufflation (MI-E) uses positive and negative pressures to assist weak cough and help clear airway secretions. Laryngeal visualization during MI-E has revealed that inappropriate upper airway responses can impede its efficacy. However, the dynamics of pressure transmission in the upper airways during MI-E is unclear, as are the relationships between anatomical structure, pressure and airflow. Can airflow resistance through the upper airway and the larynx feasibly be calculated during MI-E, and if so, how are the pressures transmitted to the trachea? Cross-sectional study of ten healthy adults, where MI-E was provided with and without active cough, employing pressure settings +20/-40 and ±40 cmH2O. Airflow and pressure at the level of the facemask were measured using a pneumotachograph, while pressure transducers (positioned via transnasal fiberoptic laryngoscopy) recorded pressures above the larynx and within the trachea. Upper airway resistance (Ruaw) and translaryngeal resistance (Rtl) were calculated (cmH2O/L/sec) and compared to direct observations via laryngoscopy. Positive pressures reached the trachea effectively, while negative tracheal pressures during exsufflation were approximately half of the intended settings. Insufflation pressure increased slightly when passing through the larynx. Participant effort influenced tracheal pressures and the resistances, with findings consistent with laryngoscopic observations. During MI-E, resistance appears dynamic, with Ruaw exceeding Rtl. Inappropriate laryngeal closure increased Rtl during both positive and negative pressures. Upper airway and translaryngeal resistance can feasibly be calculated during MI-E. The findings indicate different transmission dynamics for positive and negative pressures, and that resistances are influenced by participant effort. The findings support using lower insufflation pressures and higher negative pressures in clinical practice.

Two-year survival after scheduled extubation in patients with pneumonia or ARDS: a prospective observational study

PurposeTo report two-year survival after scheduled extubation in patients with pneumonia or acute respiratory distress syndrome (ARDS).MethodsThis was a prospective observational study performed in a respiratory ICU of a teaching hospital. Pneumonia or ARDS patients who successfully completed a spontaneous breathing trial were enrolled. Data were collected before extubation. Patients were followed up to two years by phone every 3 months.ResultsA total of 230 patients were enrolled in final analysis. One-, 3-, 6-, 12-, and 24-month survival was 77.4%, 63.8%, 61.3%, 57.8%, and 47.8%, respectively. Cox regression shows that Charlson comorbidity index (hazard ratio: 1.20, 95% confidence interval: 1.10–1.32), APACHE II score before extubation (1.11, 1.05–1.17), cough peak flow before extubation (0.993, 0.986–0.999), and extubation failure (3.96, 2.51–6.24) were associated with two-year mortality. To predict death within two years, the area under the curve of receiver operating characteristic was 0.79 tested by Charlson comorbidity index, 0.75 tested by APACHE II score, and 0.75 tested by cough peak flow. Two-year survival was 31% and 77% in patients with Charlson comorbidity index ≥ 1 and < 1, 28% and 62% in patients with APACHE II score ≥ 12 and < 12, and 64% and 17% in patients with cough peak flow > 58 and ≤ 58 L/min, respectively.ConclusionsComorbidity, disease severity, weak cough and extubation failure were associated with increased two-year mortality in pneumonia or ARDS patients who experienced scheduled extubation. It provides objective information to caregivers to improve decision-making process during hospitalization and post discharge.

A Case of Infant Botulism Treated with Human-Derived Antitoxin

Background: Infant botulism is a severe and rare illness due to the ingestion of the neurotoxin secreted by Clostridium botulinum and is a neuroparalytic descendant acute disease which is reversible, treatable and preventable. Symptoms vary from mild hypotonia to respiratory failure and sudden death. Clinical Observation: A four-months-old female baby taken to the Emergency Room because of hypoactivity and failure to eat. Parents reported constipation for the last 5 days. The physical examination showed a hypoactive baby with sleep tendency and mild axial hypotonia. During the next 48 hours there is a progressive worsening of the clinical condition with severe axial hypotonia, generalized weakness, weak cry, increasing difficulty in sucking and swallowing and increase of respiratory secretions together with weak cough reflex. An electromyogram was performed with normal results. Parents denied giving the baby honey, infusions or any other food other than milk or cereals. Although there was no clear epidemiological history, infant botulism was suspected, and contact was made with the local Health Department and a direct toxin analysis was requested from blood and fecal samples. She received treatment with human derived botulism antitoxin (BabyBIG®) with a favorable outcome. The diagnosis was confirmed by the detection of the botulism toxin B in the patient's stools. Comments: Infant botulism, although it is a rare disease in our environment, requires a high level of suspicion to make an early diagnosis and initiate a timely and specific treatment and thus reduce complications and the course of the disease.

Pilot observational cohort study to determine whether waveform and flow traces from mechanical insufflation–exsufflation (MI-E) can be used to identify laryngeal responses to MI-E and thus optimise treatment algorithms in neuromuscular patients in a tertiary centre: a protocol description

IntroductionPatients with neuromuscular disease often have a weak and ineffective cough due to respiratory muscle weakness. One treatment option is mechanical insufflation–exsufflation (MI-E), also known as cough assist, which is...

Risk Factors of Non-Invasive Ventilation Failure in COPD Patients Presenting with Acute Exacerbation

Background: Non-invasive ventilation (NIV) is the first-line management for acute exacerbation of COPD (AECOPD), but some patients don’t improve and need invasive ventilation, leading to high mortality. We conducted a study to determine risk factors associated with NIV outcomes in these patients. Identifying predictive parameters of NIV failure could help timely intervention and prevent mortality. Methods: A Quasi Single Arm study was conducted at a tertiary care Hospital, in Karachi, from July to December 2022. We studied 170 COPD patients admitted to Medicine Department and Medical ICU with acute respiratory failure, among those 170 patients 80 were male and 90 were female, aged above 40 and below 80 years. Results: Among 170 AECOPD patients studied, 38% experienced NIV failure, while 61% had NIV success. In the NIV failure group, 38.46% of patients died in hospital. Most factors like quadrant infiltrate, weak cough reflex, low consciousness level, more requirements of oxygen, low pH, more respiratory rate, and positive blood cultures (p-value &lt;0.001) were significantly associated with NIV failure and mortality, while others with no significant association still contributed towards NIV failure, like co-morbidities. Out of the 66 patients with NIV failure, 56% experienced immediate failure, 33% had early NIV failure, and 11% had late NIV failure. Conclusion: Most identified risk factors significantly predicted NIV failure, suggesting they may serve as useful early indicators to guide intervention. Even non-significant factors still exhibited some association with NIV failure. Further research exploring additional predictors could optimize NIV outcomes and reduce mortality from AECOPD.

Factors associated with extubation failure in an intensive care unit: a case-control study.

to investigate the factors associated with extubation failure of patients in the intensive care unit. unpaired, longitudinal, retrospective and quantitative case-control with the participation of 480 patients through clinical parameters for ventilator weaning. Data were analyzed by: Fisher's exact test or the chi-square test; unpaired two-tailed Student's t test; and Mann-Whitney test. Significant P values lower than or equal to 0.05 were admitted. of the patients, 415 (86.5%) were successful and 65 (13.5%) failed. Success group: the most negative fluid balance, APACHE II in 20 (14-25), weak cough in 58 (13.9%). Failure group: the most positive fluid balance, APACHE II in 23 (19-29), weak cough in 31 (47.7%), abundant amount of pulmonary secretions in 47.7%. positive fluid balance and the presence of inefficient cough or inability to clear the airway were predictors of extubation failure.

Expert Consensus on Clinical Decision Making in the Disease Trajectory of Oropharyngeal Dysphagia in Adults: An International Delphi Study.

To date, no consensus exists on the complex clinical decision-making processes involved in oropharyngeal dysphagia, or swallowing disorders. This study aimed to develop an international consensus on a clinical decision tree for the disease trajectory of oropharyngeal dysphagia in adults, taking into account physiological impairments of swallowing, risk factors for the development of complications from oropharyngeal dysphagia, and prognostic factors for treatment outcomes. Using the Delphi technique, consensus was achieved among dysphagia experts across 31 countries, resulting in a total of 10 physiological impairments, 23 risk factors and 21 prognostic factors identified as relevant factors in the clinical decision-making process. Factors most contributing to the severity of oropharyngeal dysphagia were 'Aspiration', 'Incomplete ejection or failure to eject aspirated materials from the airways', 'Weak or absent cough', 'Choking' and 'Sensory deficits in the oropharynx'. To connect the existing theoretical framework to clinical practice, future research will develop the current findings by corroborating the domains based on relevant factors for clinical decision making and those that contribute to the severity of oropharyngeal dysphagia.

Airway Clearance Strategies and Secretion Management in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative motor neuron disease that affects voluntary muscle movement. Often, difficulty in coughing, breathing, and swallowing are sequela associated with the condition, and the presence of bulbar muscle predominant weakness results in deleterious effects on airway clearance and secretion management. This narrative review will provide practical guidance for clinicians treating this population. Cough insufficiency in this population typically manifests as a prolonged, slow, weak cough effort that impedes the clearability of secretions and airway protection. Dystussia and dysphagia frequently occur simultaneously in bulbar dysfunction, subsequently impacting respiratory health. Measures of respiratory strength should be obtained and monitored every 3-6 months, preferably in a multidisciplinary clinic setting. Cough augmentation, whether manual or mechanical techniques, should be sought as early in the disease progression as possible to adequately control secretions in the proximal airways. This airway clearance strategy can aid in the prevention and treatment of respiratory tract infections (RTIs), which can pose a significant clinical hurdle to those with ALS. The use of mechanical insufflation-exsufflation may be complicated by severe bulbar dysfunction rendering this technique ineffective. Though peripheral airway clearance strategies, such as high-frequency chest-wall compression, have the advantage of being less impacted by bulbar dysfunction, it is only recommended this modality be used in conjunction with, versus in lieu of, proximal strategies. Salivary secretion management includes the use of anticholinergics, botulinum toxin, and radiation therapy depending on severity and desire for relief.

Relationship between orofacial dysfunction and orofacial features, oral function, and eating performance among preschool children

Background/purposeOrofacial (OF) development is influenced by multiple factors. This study aimed to explore the relationship between OF dysfunction (OFD) and OF features, oral function, and eating performance among preschool children. Materials and methodsThere were 243 preschool children and their parents who participated in this cross-sectional study. Participant demographic information and eating performance were obtained from questionnaires completed by their mothers. OF features and functions were assessed using oral examinations. OFD assessments were performed using Nordic Orofacial Test–Screening (NOT-S). ResultsApproximately 80% of participants had at least one domain of NOT-S affected. The main OFD in a structured interview was chewing and swallowing (64.61%). Dysarthria (40.38%), weak bite force (53.85%), inability to effectively chew (45.19%), and taking longer than 30 min to eat meals (75.00%) were significantly more prevalent among participants with OFD than among those without OFD (all P < 0.05). Also, compared with participants born full-term, those born prematurely and who had OFD had higher rates of V-shaped dental arch (42.11%), high-arched palate (31.58%), small mouth opening capacity (7.89%), dysarthria (65.79%), preference to eating soft-textured food (42.11%), and weak cough strength (21.05%). Taking longer than 30 min to eat meals (adjusted odds ratio (AOR = 8.87, P < 0.001) and not effectively chewing food (AOR = 8.81, P < 0.001) were significantly associated with OFD. ConclusionChewing and swallowing and habits are common among preschool children and associated with OFD. OFD is associated with OF features, and presented in oral function and eating performance.

Arthrogryposis multiplex congenita in a child with congenital fractures: a case report

BackgroundBruck syndrome is an exceedingly rare form of osteogenesis imperfecta, inherited autosomal recessively and presenting with the concurrence of bone fragility and congenital contractures of large joints. The disease usually progresses relentlessly to result in recurrent fractures, short stature, severe kyphoscoliosis, and susceptibility to recurrent respiratory tract infections.Case presentationThe index child was a male newborn to healthy, nonconsanguineous, Sinhalese parents. The child had multiple contractures involving all large joints with pterigium formation in addition to congenital fractures involving left humerus and ulna at birth. The phenotypic features in this child were highly suggestive of Bruck syndrome. Genetic counseling was offered to the parents, although specific genetic testing could not be undertaken due to lack of resources. Bone and skin biopsy were not performed since only palliative care was possible. Over the course, he developed recurrent severe chest infections due to poor muscle tone, weak cough reflex, and pooling of secretions. Unfortunately, he succumbed at the age of 7 months following severe pneumonia.ConclusionThe association of arthrogryposis with osteogenesis imperfecta is extremely rare and known as Bruck syndrome. Early diagnosis during the antenatal period is helpful in genetic counseling, assessment of severity, and exploration of therapeutic options

P.40 The importance of bulbar/respiratory symptoms in spinal muscular atrophy: results from interviews with patients, caregivers and healthcare providers

Motor function is regularly assessed in clinical practice, but bulbar difficulties are less understood or monitored among people living with spinal muscular atrophy (plwSMA). To understand how plwSWA experience bulbar/respiratory difficulties and to identify preferences for monitoring them, a mixed-methods study was conducted with plwSMA (Types 2/3, aged 5–60 years, untreated and people on any therapy) and healthcare providers (HCPs) using an online questionnaire, qualitative interviews and focus groups. PlwSMA (N=30) and HCPs (N=7) were interviewed. PlwSMA included adults (n=9), adolescents and their caregivers (n=12), and children (n=9; interviews with caregivers). The results of these interactions showed that plwSMA with breathing difficulties (n=11/30) most often experienced a weak cough and sleep hypopnea. HCPs reported that plwSMA experienced difficulties taking a deep breath and breathing comfortably without respiratory support. PlwSMA with swallowing difficulties (n=13/30) most often reported needing to chew food longer, difficulties swallowing food, coughing while swallowing, and weak swallowing. HCPs also reported that plwSMA experienced these difficulties; however, additional difficulties, such as swallowing liquids, choking, and becoming fatigued were commonly mentioned. PlwSMA preferred measuring shortness of breath, blood oxygen levels, caloric intake, cough/swallow strength, and digestion. PlwSMA spontaneously mentioned that quality of sleep impacted energy level and a broad range of functional abilities. These results provide evidence of various difficulties commonly experienced among plwSMA (Types 2/3). Meaningful aspects of health related to bulbar function may not be fully captured by current assessments in routine clinical practice. Interviewees indicated that developing in-home remote monitoring tools can provide healthcare teams with essential information about bulbar/respiratory function and contribute to better health monitoring of plwSMA.

Weak cough is associated with increased mortality in COPD patients with scheduled extubation: a two-year follow-up study

BackgroundCough strength is associated with short-term outcome in patients with scheduled extubation who successfully complete a spontaneous breathing trial (SBT). However, the long-term outcome is unclear.MethodsThis was a prospective observational study performed in a respiratory ICU of a teaching hospital. COPD patients who successfully completed a SBT were candidates. We enrolled the case who assessed the cough strength by cough peak flow (CPF) or semiquantitative cough strength score (SCSS, ranging from 0 = weak to 5 = strong). Patients were followed up to two years by phone every 3 months.ResultsA total of 215 patients were enrolled in current study. Among them, CPF and SCSS were measured in 214 and 208 cases, respectively. Strong cough was associated with a 16% decrease in the risk of two-year mortality (adjusted hazard ratio [HR] 0.84, 95%CI: 0.78–0.91) per 10 L/min increment of CPF. When it was tested by SCSS, decrease in the risk of two-year mortality per unit increment was 27% (adjusted HR 0.73, 95%CI: 0.62–0.86). Similar results were confirmed in the discharged patients. In all patients, the two-year mortality was 75%, 53%, and 38% in patients with CPF < 60, 60–90, and > 90 L/min; and 85%, 70%, and 40% in patients with SCSS of 0–1, 2–3, and 4–5, respectively. Similar trend was found among the discharged patients whether it was assessed by CPF or SCSS.ConclusionsIn COPD patients, weak cough is associated with increased two-year mortality after a scheduled extubation. It provides objective information to caregivers to improve decision-making process during hospitalization and after discharge.

Changes in ventilation distribution in children with neuromuscular disease using the insufflator/exsufflator technique: an observational study

Patients with neuromuscular disease often suffer from weak and ineffective cough resulting in mucus retention and increased risk for chest infections. Different airway clearance techniques have been proposed, one of them being the insufflator/exsufflator technique. So far, the immediate physiological effects of the insufflator/exsufflator technique on ventilation distribution and lung volumes are not known. We aimed to describe the immediate effects of the insufflator/exsufflator technique on different lung volumes, forced flows and ventilation distribution. Eight subjects (age 5.8–15.2 years) performed lung function tests including spirometry, multiple breath washout and electrical impedance tomography before and after a regular a chest physiotherapy session with an insufflator/exsufflator device. Forced lung volumes and flows as well as parameters of ventilation distribution derived from multiple breath washout and electrical impedance tomography were compared to assess the short-term effect of the therapy. In this small group of stable paediatric subjects with neuromuscular disease we could not demonstrate any short-term effects of insufflation/exsufflation manoeuvres on lung volumes, expiratory flows and ventilation distribution. With the currently used protocol of the insufflation/exsufflation manoeuvre, we cannot demonstrate any immediate changes in lung function.

A Review on Vocal Cord Palsy: Complications and Management

Vocal cord paralysis is a multifaceted problem that affects people of all ages and is initially diagnosed by various healthcare providers. It is a common condition that occurs due to the obstruction of nerve impulses from the brain to the voice box. It ranges from slight hoarseness to fatal, life-threatening complications. To get to the exact diagnosis, determining the etiology of paralysis is essential. For restoration of normal function, accurate diagnosis has proven to be helpful. Vocal cord paralysis (VCP) is a. reasonably common condition caused by a vagus nerve or its recurrent laryngeal nerve branch disease process. The nerve’s longer length causes increased vulnerability. Peripheral lesions to the vagus are responsible for 90% of VCP (Vocal cord paralysis). Etiology includes scarring due to intubation or inflammatory disorders, iatrogenic causes like surgical traumas, malignancy, CNS pathologies like stroke, CNS tumors, and systemic diseases like ALS, Guillain barre syndrome. Vocal cord paralysis can cause consequences such as a weak cough, trouble swallowing, dysphagia, stridor, hoarseness, aspiration risk, granuloma formation, airway blockage, and a lower quality of life. Various treatment modalities like tracheostomy, usage of botulinum toxin, adenoidectomy, cordotomy, reinnervation, and gene therapy are used. For this narrative review, a literature search was undertaken using "unilateral and bilateral vocal cord palsy" and "dysphagia" in the Pubmed, Medline, and Embase databases. Bilateral vocal cord paralysis is a problematic and distressing condition that affects both adults and children. Surgical procedures such as tracheostomy, adenoidectomy, cordotomy, and laryngeal reinnervation have been used to treat this condition successfully. Treatment modalities should be individualized according to the patient's clinical features and physician's expertise.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disordercharacterised by progressivemuscle weakness beginning in early childhood.Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis,pneumonia, or the need for ventilatory support.There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weaknessin general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,and two trialsregistersto 23 March2021,together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria.We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane.We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC andhospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function,forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenoneon respiratory function compared to placebo. The trial that contributed numerical data includedpatientswith a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion,with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome,idebenonemay resultin less of a decline from baseline inFEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) andPEF(MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenonewas associated with fewer serious adverse events(RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) andlittle to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo.Idebenonemay result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexorsand MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacyanalysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenonemay result in slightly less of a decline in FVCandless of a decline inFEV1andPEF, but probably has little to no measurable effect on change in quality of life. Idebenoneis associated with fewer serious adverse events than placebo. Idebenonemay result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data.Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disordercharacterised by progressivemuscle weakness beginning in early childhood.Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis,pneumonia, or the need for ventilatory support.There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weaknessin general, and respiratory decline in particular. OBJECTIVES: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,and two trialsregistersto 23 March2021,together with reference checking, citation searching, and contact with study authors to identify additional studies. We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria.We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane.We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC andhospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function,forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). MAIN RESULTS: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenoneon respiratory function compared to placebo. The trial that contributed numerical data includedpatientswith a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion,with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97; 64 participants; low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49; 63 participants; moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome,idebenonemay resultin less of a decline from baseline inFEV1 (MD 8.28%, 95% CI 0.89 to 15.67; 53 participants) andPEF(MD 6.27%, 95% CI 0.61 to 11.93; 1 trial, 64 participants) compared to placebo. Idebenonewas associated with fewer serious adverse events(RR 0.42, 95% CI 0.09 to 2.04; 66 participants; low-certainty evidence) andlittle to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13; 66 participants; low-certainty evidence) compared to placebo.Idebenonemay result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexorsand MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors; both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants, for which data were available only as a press release without numerical data, was prematurely discontinued due to futility after an interim efficacyanalysis based on FVC. There were no safety concerns. The certainty of the evidence was low for most outcomes due to imprecision and publication bias (the lack of a full report of the larger trial, which was prematurely terminated). Idebenone is the only antioxidant agent tested in RCTs for preventing respiratory decline in people with DMD for which evidence was available for assessment. Idebenonemay result in slightly less of a decline in FVCandless of a decline inFEV1andPEF, but probably has little to no measurable effect on change in quality of life. Idebenoneis associated with fewer serious adverse events than placebo. Idebenonemay result in little to no difference in change in muscle function. Discontinuation due to the futility of the SIDEROS trial and its expanded access programmes may indicate that idebenone research in this condition is no longer needed, but we await the trial data.Further research is needed to establish the effect of different antioxidant agents on preventing respiratory decline in people with DMD during the respiratory decline phase of the condition.

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

BackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionsWeak 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.

COVID-19 in children with neuromuscular disorders.

ObjectiveChildren with neuromuscular disorders have been assumed to be a particularly vulnerable population since the beginning of COVID-19. Although this is a plausible hypothesis, there is no evidence that complications or mortality rates in neuromuscular patients are higher than in the general population. The aim of this study is to describe the clinical characteristics and outcome of COVID-19 in children with neuromuscular disorders. MethodsA registry of children with neuromuscular conditions and laboratory-confirmed-SARS-CoV-2 infection was set up by the Neuromuscular Working Group of the Spanish Pediatric Neurology Society (SENEP). Data to be collected were focused on the characteristics and baseline status of the neuromuscular condition and the course of COVID-19. ResultsSevere complications were not observed in our series of 29 children with neuromuscular disorders infected by SARS-CoV-2. Eighty-nine percent of patients were clinically categorized as asymptomatic or mild cases and 10% as moderate cases. Patients with a relatively more severe course of COVID-19 had SMA type 1 and were between 1 and 3 years.ConclusionsThe course of COVID-19 in children with neuromuscular disorders may not be as severe as expected. The protective role of young age seems to outweigh the risk factors that are common in neuromuscular patients, such as a decreased respiratory capacity or a weak cough. Further studies are needed to know if this finding can be generalized to children with other chronic diseases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-020-10339-y.