Mechanical Insufflation-Exsufflation: The Rest of the Story.

Mechanical insufflation-exsufflation has been reported to decrease pneumonia rates by about 90% for patients with Duchenne muscular dystrophy now living into their 40s and 50s without tracheotomy tubes. It greatly reduces respiratory complications and hospitalization rates to less than one per 10 patient-years for advanced spinal muscular atrophy type 1, through 25-30 years of age. It is most successful from the point at which small children become able to cooperate with it, generally from 3 to 5 years of age. However, since the 1950s, successful use to extubate and decannulate ventilator "unweanable" patients with little to no measurable vital capacity without resorting to tracheostomy has always been at pressures of 50-60 cm H2O via oronasal interfaces and at 60-70 cm H2O via airway tubes when present. It must usually also be used in conjunction with up to continuous noninvasive positive pressure ventilatory support. Centers that use these effectively have eliminated need to resort to tracheotomies for people with muscular dystrophies and spinal muscular atrophies, including unmedicated patients with spinal muscular atrophy type 1. Barotrauma has been rare despite dependence on it and noninvasive ventilatory support. Despite this, noninvasive respiratory management continues to be widely underutilized.

Effects of Modified Diaphragmatic Training on Gastroesophageal Reflux Disease Questionnaire Score, Diaphragmatic Excursion, and Maximum Inspiratory Pressure in Adults with Gastroesophageal Reflux Disease After COVID-19: A Single-Blinded Randomized Control.

BACKGROUND: Although diaphragmatic training has been shown to improve gastroesophageal reflux disease (GERD) symptoms, its effectiveness in adults with GERD after COVID-19 has not been evaluated. This study examined the effectiveness of modified diaphragmatic training (MDT) on GERD questionnaire (GERDQ) score, diaphragmatic excursion, and maximum inspiratory pressure (MIP) in adults with GERD after COVID-19. METHODS: This single-blinded randomized control trial was conducted at Persahabatan Hospital from February to April 2023. The medical records of 364 patients with persistent gastrointestinal symptoms were evaluated; among these potential participants, 302 had symptoms before, and 62 after, COVID-19 infection. Fifty of these patients fulfilled the study inclusion and exclusion criteria and were randomly assigned to the intervention (n = 25) or control (n = 25) groups. Four weeks of diaphragmatic training were followed by MDT or standard diaphragmatic training. A follow-up assessment was conducted 30 days after the beginning of the training. RESULTS: The GERDQ score was significantly decreased in the pre-post-intervention group (10.44 ± 2.00 vs 1.84 ± 2.17) and the control group (8.64 ± 0.57 vs 3.32 ± 1.49), with p < 0.001. The intervention group showed significant improvements in the right diaphragmatic excursion (RDE) (44% vs 11.87%), left diaphragmatic excursion (LDE) (46.61% vs 13.62%), and MIP (75.26% vs 23.97%) compared with the control group. CONCLUSION: MDT in adults after COVID-19 with GERD enhanced diaphragmatic excursion and MIP and decreased symptoms of gastroesophageal reflux by 8.60 points of GERDQ. Respiratory symptoms and other side effects were comparable between the groups.

Pulmonary rehabilitation in high cervical spinal cord injury: a series of 133 consecutive cases.

STUDY DESIGN: This is a retrospective study. OBJECTIVES: To detail respiratory management after a high cervical spinal cord injury (HCSCI). SETTING: A tertiary university hospital's pulmonary rehabilitation center to which most individuals with HCSCI and ventilatory insufficiency throughout Korea are referred. METHODS: The medical records of individuals with complete or sensory incomplete HCSCI admitted to the pulmonary rehabilitation center and receiving the center's standard treatment were retrospectively reviewed, focusing on respiratory state transitions. RESULTS: In total, 133 individuals with a C1-4 neurological level of injury (A: 101 or B: 32 on the American Spinal Injury Association Impairment Scale) were identified; 110 (82.7%) had indwelling tracheostomy tubes at admission and 75 underwent successful decannulation during admission. At the final follow-up, 76 individuals (57.1%) still required mechanical ventilation (MV) and 37 (27.8%) still required indwelling tracheostomy tubes. Of the individuals who had tracheostomy tubes without ventilatory support, 30 underwent decannulation and were discharged without non-invasive MV support. Of those with MV via tracheostomy on admission, 25 were switched to non-invasive MV after decannulation. CONCLUSION: Respiratory management in complete or sensory incomplete HCSCI needs to be determined by reflecting the current ventilatory state with a comprehensive evaluation of pulmonary function and ventilatory state monitoring. Pulmonary rehabilitation in individuals with HCSCI should be emphasized in the aspect of improving quality of life by avoiding unwanted tracheostomy and changing management methods depending on their recovery.

Clinical Implications of Assisted Peak Cough Flow Measured With an External Glottic Control Device for Tracheostomy Decannulation in Patients With Neuromuscular Diseases and Cervical Spinal Cord Injuries: A Pilot Study.

OBJECTIVE: To investigate the clinical usefulness and significance of an external control device substituting for glottic function in determining the feasibility of decannulation in tracheostomized patients with neuromuscular diseases and cervical spinal cord injuries whose assisted peak cough flow (APCF) was unmeasurable or <160L/min. DESIGN: Before-after trial. SETTING: Inpatient setting in a university hospital. PARTICIPANTS: Tracheostomized patients (N=16; 11 with neuromuscular diseases and 5 with cervical spinal cord injuries) were recruited. INTERVENTIONS: Unassisted peak cough flow (UPCF) and APCF were measured with and without an external glottic control device. Among patients whose APCF without the device was <160L/min, if their APCF with the device was measured as ≥160L/min, they were decannulated. After decannulation, UPCF and APCF were measured again. MAIN OUTCOME MEASURES: APCF with and without an external glottic control device as well as APCF after decannulation. RESULTS: After successful decannulation, APCFs were greater than or equal to those measured with the device before decannulation. No patients underwent intubation or retracheostomy, and there were no respiratory complications. CONCLUSIONS: The external glottic control device substituting for innate glottic function is beneficial for determining tracheostomy decannulation. It provides an objective and accurate APCF. It is particularly helpful for patients whose APCF is ≥160L/min while using the device, even if APCF is <160L/min without this device.

Management of Ventilatory Insufficiency in Neuromuscular Patients Using Mechanical Ventilator Supported by the Korean Government.

Since 2001, financial support has been provided for all patients with neuromuscular disease (NMD) who require ventilatory support due to the paralysis of respiratory muscles in Korea. The purpose of this study was to identify ventilator usage status and appropriateness in these patients. We included 992 subjects with rare and incurable NMD registered for ventilator rental fee support. From 21 February 2011 to 17 January 2013, ventilator usage information, regular follow-up observation, and symptoms of chronic hypoventilation were surveyed by phone. Home visits were conducted for patients judged by an expert medical team to require medical examination. Abnormal ventilatory status was assessed by respiratory evaluation. Chronic respiratory insufficiency symptoms were reported by 169 of 992 subjects (17%), while 565 subjects (57%) did not receive regular respiratory evaluation. Ventilatory status was abnormal in 102 of 343 home-visit subjects (29.7%). Although 556 subjects (56%) reported 24-hour ventilator use, only 458 (46%) had an oxygen saturation monitoring device, and 305 (31%) performed an airstacking exercise. A management system that integrates ventilator usage monitoring, counselling and advice, and home visits for patients who receive ventilator support could improve the efficiency of the ventilator support project.

Postural vital capacity difference with aging in duchenne muscular dystrophy.

INTRODUCTION: A change in vital capacity (VC) from standing to supine can be an index of diaphragm paralysis if it exceeds 25%. We aimed to verify whether the postural VC difference increases with age and reflects diaphragm weakness in DMD. METHODS: VCs were measured in DMD. Postural VC difference and percentage were calculated from the VC data. Maximal inspiratory pressure (MIP) and MIP percentage were measured as an indirect index of diaphragm weakness. RESULTS: A total of 220 patients and 544 measurements were collected. MIP and MIP percentage decreased significantly with age (P < 0.001 for both). Estimated postural VC difference and percentage also decreased (P < 0.001, P = 0.006, respectively). Age group comparisons showed a significant decrease in younger, but not older subjects. CONCLUSIONS: This study shows that the postural VC difference tended to decrease with age and might not reflect diaphragmatic weakness in DMD; however, this should be interpreted cautiously.

In Vivo Reprogramming Using Yamanaka Factors in the CNS: A Scoping Review.

Central nervous system diseases, particularly neurodegenerative disorders, pose significant challenges in medicine. These conditions, characterized by progressive neuronal loss, have remained largely incurable, exacting a heavy toll on individuals and society. In recent years, in vivo reprogramming using Yamanaka factors has emerged as a promising approach for central nervous system regeneration. This technique involves introducing transcription factors, such as Oct4, Sox2, Klf4, and c-Myc, into adult cells to induce their conversion into neurons. This review summarizes the current state of in vivo reprogramming research in the central nervous system, focusing on the use of Yamanaka factors. In vivo reprogramming using Yamanaka factors has shown promising results in several animal models of central nervous system diseases. Studies have demonstrated that this approach can promote the generation of new neurons, improve functional outcomes, and reduce scar formation. However, there are still several challenges that need to be addressed before this approach can be translated into clinical practice. These challenges include optimizing the efficiency of reprogramming, understanding the cell of origin for each transcription factor, and developing methods for reprogramming in non-subventricular zone areas. Further research is needed to overcome the remaining challenges, but this approach has the potential to revolutionize the way we treat central nervous system disorders.

Mobile Apps to Improve Brace-Wearing Compliance in Patients with Idiopathic Scoliosis: A Quality Analysis, Functionality Review and Future Directions.

This study was performed to review which mHealth apps that improve brace-wearing compliance are currently available, and to carry out their quality assessments by listing their functionalities. We found ten mHealth apps in the literature review and commercial mHealth apps market (Google Play and App store). Then, the quality of these apps was evaluated by their transparency, health content, excellent technical content, security/privacy, issues of usability, and subjective ratings (THESIS) scale, and the functionalities of the included apps were reviewed. Regarding these functionalities, four categories (data acquisition, compliance enhancement, educational components, and additional functionalities) and twelve subcategories were identified. The mean overall quality of the apps was 3.00 out of 5. Although four of the apps achieved a score of 3.0 or more for their overall quality, indicating an acceptable quality, none of the apps scored higher than 4.0, which indicated a high or excellent quality. According to the sections, the transparency section had the highest rating (3.92) and the security/privacy section received the lowest rating (2.02). Given that the overall quality of current mHealth apps was not high, and their potential to motivate patients with idiopathic scoliosis to adhere to their bracing treatment, it is necessary to develop high-quality apps with appropriate functionalities for supporting brace treatment.

Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma.

OBJECTIVE: To investigate associations between total serum immunoglobulin E (IgE) levels and single nucleotide polymorphisms (SNPs) from eight candidate genes (IL-4 rs2243250, IL-4Rα rs1805010, IL-13 rs20541, IL-13Rα1 rs2495636, CD14 rs2569190, tumor necrosis factor-alpha (TNF-α) rs1800629, cytotoxic T lymphocyte-associated antigen (CTLA4) rs231775, FCER1B rs1441585) in children with asthma and to evaluate gene-gene interactions. METHODS: A total of 669 Korean children with asthma (n = 544 atopic n = 125 non-atopic) were included. Asthma phenotypes, total serum IgE levels, and methacholine challenge test results were evaluated. SNPs were genotyped using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Multi-factor dimensionality reduction (MDR) was used to analyze gene-gene interactions. RESULTS: The combination of the IL-13, IL-13Rα1, and CTLA4 polymorphisms was selected through MDR analysis of the data pertaining to children with atopic and non-atopic asthma (accuracy = 0.5459, cross validation consistency (CVC) = 10/10). The IL-4Rα, IL-13, IL-13Rα1, CD14, and CTLA4 polymorphisms were selected as the best model of increased total serum IgE levels in non-atopic and atopic asthma (asthma: accuracy = 0.4726, CVC = 10/10; atopic asthma: accuracy = 0.4573, CVC = 10/10). Both the IL-4Rα and the IL-13 polymorphisms were correlated with the IgE level. ANOVA analysis revealed that the combinations of the CTLA4 and IL-13, IL-13 and IL-13Rα1, IL-4Rα and IL-13, and CD14 and IL-13 polymorphisms were all significantly associated with increased total serum IgE levels. CONCLUSIONS: The best model of increased IgE level included the IL-4Rα, IL-13, IL-13Rα1, CD14, and CTLA4 polymorphisms. Of the various interactions between these polymorphisms, the combinations of the CTLA4 and IL-13 polymorphisms and the IL-13 and IL-13Rα1 polymorphisms showed synergistic effects in terms of increased total serum IgE levels in the present cohort.

Clinical Implications of Routine Monitoring of Pulmonary Function and Ventilation in Patients with Duchenne Muscular Dystrophy.

PURPOSE: To investigate the effect of regular monitoring of pulmonary function and ventilatory status on the initiation of non-invasive ventilation (NIV) between patients who were routinely monitored before receiving NIV and those who were not. MATERIALS AND METHODS: This retrospective cohort study included subjects with Duchenne muscular dystrophy (DMD) who first received NIV between 2010 and 2019. The subjects were assigned to either the regular-follow-up (REG) group or the non-REG group, according to their follow-up status, before initiating NIV. We compared the number of emergent cases, the results of nocturnal ventilatory monitoring, and the pulmonary function of each group at initial ventilatory support. RESULTS: In total, 73 subjects were enrolled in the REG group and 47 subjects in the non-REG group. There were significantly more emergency cases due to respiratory insufficiency in the non-REG group (12/47, 25.5%) than in the REG group (3/73, 4.1%). At the time of initial ventilatory support, hypoventilatory symptoms were more common and relatively severe in the non-REG group (37/47, 78.7%) than in the REG group (18/73, 24.7%). The average age at initial ventilatory support of the non-REG group was 2.15 years older than that of the subjects in the REG group. Moreover, subjects who were not regularly monitored exhibited greater deterioration in pulmonary function compared to those who were regularly followed up. CONCLUSION: Regular evaluation of pulmonary function and ventilatory status before the onset of ventilatory insufficiency is crucial to reduce the risk of patients with DMD requiring emergency care due to ventilatory insufficiency.

Standardization of Air Stacking as Lung Expansion Therapy for Patients With Restrictive Lung Disease: A Pilot Study.

OBJECTIVE: Although air stacking is a widely used lung expansion therapy essential for restrictive lung diseases, important details such as peak insufflation pressure (PIP) and number of squeezes have not been investigated. The purpose of this study was to standardize a method of air stacking to minimize problems with its application by identifying the optimal pressure and number of squeezes performed by professional physicians and investigating the current status of routine air stacking implementation in patients. METHODS: This prospective cross-sectional test-retest study involved individuals who had neuromuscular disorders and had performed air stacking exercise for longer than 1 year. PIP and number of squeezes were measured to identify the differences between caregivers and physicians. Cases of incorrectly performed air stacking were investigated and categorized. The problems associated with air stacking were evaluated. RESULTS: A total of 45 participants were included. PIP was 41.4 (SD = 4.2; range = 34.8-50.0) cm H2O, and optimal number of squeezes was 3.1 (SD = 0.5; range = 2-4). When the air stacking methods used by caregivers were evaluated, 19 of 45 caregivers (42.2%) used methods inappropriately. Higher PIP and larger number of squeezes were observed with caregiver implementation. Thirty caregivers (66.7%) experienced finger or wrist pain; this problem was observed especially in female caregivers, who tended to incorrectly perform air stacking. CONCLUSIONS: This pilot study showed that the optimal pressure of air stacking was 35 to 50 cm H2O. Caregivers often perform air stacking inappropriately, leading to complications without achieving the purpose of air stacking. The introduction of a new method, such as manometry, can be helpful for achieving optimal air stacking. IMPACT: Optimal pressure of air stacking can be measured with inexpensive, simple, and commercially available digital manometry. This approach enables air stacking to be performed and taught more accurately and efficiently and reduces complications in both patients and caregivers.

The association between cardiac involvement and long-term clinical outcomes in patients with Duchenne muscular dystrophy.

AIMS: Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long-term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long-term clinical outcomes and their associated factors in patients with late-stage DMD. METHODS AND RESULTS: A total of 116 patients with late-stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all-cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow-up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log-rank P = 0.005). In the multivariable Cox regression analysis, brain-natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019-1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651-52.148, P = 0.011) were significant predictors of all-cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log-rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005-1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704-10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. CONCLUSIONS: Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late-stage DMD, irrespective of LVEF.

Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma.

Activation of the prostaglandin D2 receptor (PTGDR) may contribute to pulmonary vasodilation, bronchoconstriction, recruitment of eosinophils, basophils and T-lymphocytes, and enhanced synthesis of leukotriene C4. We investigated whether polymorphisms of the leukotriene C4 synthase (LTC4S) -444A/C and PTGDR -441T/C were associated with clinical phenotypes and responsiveness to leukotriene receptor antagonist (LTRA) in Korean asthmatic children. We enrolled 270 normal and 870 asthmatic children. We prescribed montelukast (5 mg per day) to 100 of asthmatic children, and analyzed the responsiveness to LTRA by exercise challenge tests. Polymorphisms were genotyped by PCR-restriction fragment length polymorphism. As the number of minor alleles of the PTGDR -441T/C and LTC4S -444A/C polymorphisms increased, the log total eosinophil counts increased in atopic asthmatic children (P-value=0.03). We found a significant association between responsiveness to montelukast and the PTGDR polymorphism (P-value=0.038). However, the LTC4S -444A/C and PTGDR -441T/C were not associated with the susceptibility for asthma (LTC4S, AA versus AC+CC, adjusted odds ratio of 0.98 (95% confidence interval, 0.73-1.31); PTGDR, TT versus TC+CC, adjusted odds ratio of 0.90 (95% confidence interval, 0.68-1.19)) or clinical phenotypes (P-value>0.05). The effects of the PTGDR and LTC4S polymorphisms on the enhancement of eosinophil counts were additive in the Korean children with asthma. In addition, the PTGDR polymorphism seems to be associated with the responsiveness to LTRA. Therefore, therapies that target the PTGDR may be useful for modulating the responsiveness to LTRA.

Clinical Course of Amyotrophic Lateral Sclerosis according to Initial Symptoms: An Analysis of 500 Cases.

PURPOSE: One obstacle in early diagnosis of amyotrophic lateral sclerosis (ALS) is its vague initial presentation, which is generally classified into limb- and bulbar-dominant types and may be mistaken for other musculoskeletal conditions. We analyzed clinical data from patients in relation to their initial presentation and prognosis from symptom onset to diagnosis. MATERIALS AND METHODS: We retrospectively analyzed the medical records of patients with ALS who were admitted for pulmonary rehabilitation between January 2007 and December 2019. We collected data on time of onset, initial presenting symptoms, unnecessary operations due to misdiagnosis, and the time between symptom onset and final diagnosis of ALS. RESULTS: Among 500 patients, unnecessary operations were performed in 43 patients. The median durations between symptom onset and ALS diagnosis for patients with and without operations were 11 and 9 months, respectively (p=0.008). 67.0%, 28.8%, and 4.2% of the patients presented with limb-, bulbar-, and respiratory-dominant symptoms, respectively, as initial presentations. The median ages at symptom onset were significantly different for limb-, bulbar-, and respiratory-dominant onset (57.5, 60.6, and 66.7 years, respectively; p<0.001). Compared to the other two types, patients with the respiratory-dominant onset were all male and showed higher rate of emergent endotracheal intubation before ALS diagnosis. CONCLUSION: Inappropriate operations significantly delayed the diagnosis of ALS. Respiratory difficulty can account for a significant proportion among initial presentations in ALS. Compared to limb- and bulbar-dominant types, respiratory-dominant onset appears to show male predominance, older age at symptom onset, and poor respiratory prognosis.

Analysis of Pneumothorax in Noninvasive Ventilator Users With Duchenne Muscular Dystrophy.

BACKGROUND: With the advancement of cardiorespiratory interventions, the survival rate among patients with Duchenne muscular dystrophy (DMD) has increased. Subsequently, pneumothorax has become a significant problem in patients with prolonged ventilatory support. RESEARCH QUESTION: What are the frequency, recurrence rate, risk factors, and prognosis of pneumothorax in patients with DMD requiring noninvasive ventilation (NIV)? Also, are there known risk factors of pneumothorax on chest CT scans? STUDY DESIGN AND METHODS: This retrospective longitudinal cohort study included 176 patients treated between 2006 and 2019. We collected information regarding location, severity, treatment methods, recurrence frequency, abnormal findings on CT scanning, and date of death. We compared the pneumothorax and nonpneumothorax groups. We calculated the estimated survival probabilities from the age at NIV application according to pneumothorax occurrence. RESULTS: Sixteen of the 176 patients (9.0%) experienced pneumothorax (median age at diagnosis, 24.6 years; range, 20.7-33.7 years). Among the 16 patients, 15 demonstrated pneumothorax after NIV application (median time between diagnosis and initial NIV application, 5.6 years; range, 3 days-9.6 years). Sixteen patients experienced 31 episodes of pneumothoraces (range, one-five episodes); among them, seven episodes (22.6%) were asymptomatic. Known risk factors not clearly visible by radiography scans were found in chest CT scan in 11 patients (68.8%). Seven of 16 patients (43.8%) eventually sustained severe lung damage with pulmonary fibrosis. No significant between-group differences were found in body weight, BMI, and age at NIV application; however, the pneumothorax group showed a significantly higher mortality rate after NIV application. INTERPRETATION: On pneumothorax occurrence in patients with DMD, recurrences and severe lung damage are common; moreover, these patients show higher mortality rates than patients without pneumothorax. Chest CT scans should be performed to identify risk factors, and treatment should be initiated accordingly. In addition, physicians should consider chest CT scanning in the case of suspected pneumothorax, even if no radiographic abnormality is found.

Correlation of Bone Mineral Density with Pulmonary Function in Advanced Duchenne Muscular Dystrophy.

BACKGROUND: A relationship between bone mineral density (BMD) and physical function has been revealed in the general population and various diseases. However, there is a lack of research investigating the correlation between BMD and respiratory function, one of few measurable physical parameters in patients with advanced Duchenne muscular dystrophy (DMD). OBJECTIVE: To determine whether pulmonary function parameters, including respiratory muscle strength, are related to BMD. DESIGN: Retrospective observational study. SETTING: A tertiary university hospital. PATIENTS: DMD patients who were over 20 years of age, nonambulatory, and supported by mechanical ventilators. METHODS: The patients' age, weight, and pulmonary function as well as the BMD of the first and the fourth lumbar vertebra were assessed. Pulmonary function includes forced vital capacity (FVC), unassisted and assisted peak cough flow (UPCF and APCF), maximal expiratory pressure (MEP), and maximal inspiratory pressure (MIP). MAIN OUTCOME MEASURES: A bivariate correlation for BMD and other pulmonary parameters was calculated, and hierarchical regression analysis was used to determine predictors of spine Z-score. RESULTS: It was observed that the decrease in the spine BMD was not significantly correlated with age. However, the body mass index (BMI) and all parameters of pulmonary function were correlated with BMD. Partial correlation analysis adjusted by BMI showed that UPCF and APCF were powerful predictors of spine BMD. CONCLUSIONS: The BMD of the lumbar spine correlated with BMI and PCF in patients with DMD at an advanced stage.

Safety of Gastrostomy Tube Placement in Patients with Advanced Amyotrophic Lateral Sclerosis With Noninvasive Ventilation.

BACKGROUND: In patients with amyotrophic lateral sclerosis (ALS), bulbar muscle dysfunction can occur, which eventually requires the initiation of enteral tube feeding. However, there is no consensus on the optimal timing for the gastrostomy or the proper ventilator support method during the procedure. We aimed to investigate the safe range of gastrostomy according to respiratory support status and forced vital capacity (FVC) % of predicted values classification and to compare the safety of noninvasive and invasive mechanical ventilation during the procedure in ALS patients with FVC < 30% of predicted. METHODS: A total of 477 patients diagnosed with ALS at our institution from January 1, 2009, to December 31, 2018, were evaluated, and 105 patients were enrolled in this study. All medical records covering ventilation status and complications within 6 months to 1 year after the initial gastrostomy were gathered and reviewed. RESULTS: The gastrostomy procedure was considered safe regardless of FVC status or modality of respiratory support. There were complications related to the gastrostomy procedure in 6 of 105 patients and all were managed through conservative care. The incidence of complications, including respiratory ones, for noninvasive and invasive positive pressure ventilation was 5.5% and 9.6%, respectively, which were not statistically significantly different (P = .294). CONCLUSION: The procedure and tube placement of a gastrostomy can be safely performed in ALS patients with minimal FVC regardless of ventilation invasiveness. We suggest that there should be a new standard for FVC % of predicted to facilitate performing gastrostomy in ALS patients.

Clinical and genetic spectra in patients with dystrophinopathy in Korea: A single-center study.

Dystrophinopathy is a group of inherited phenotypes arising from pathogenic variants in DMD. We evaluated the clinical and genetic characteristics of Korean patients with genetically confirmed dystrophinopathy. We retrospectively reviewed medical records (January 2004-September 2020) from the myopathy database maintained at the study hospital and found 227 patients from 218 unrelated families with dystrophinopathy. Clinical phenotypes included 120 (53%) Duchenne muscular dystrophy (DMD) cases, 20 (9%) intermediate phenotype muscular dystrophy (IMD) cases, 65 (29%) Becker muscular dystrophy (BMD) cases, 18 (8%) undetermined phenotypes, and 4 (2%) symptomatic carriers. The median ages at symptom onset and diagnosis were 5.0 years (interquartile range [IQR]: 3.8-8.0) and 12.0 years (IQR: 7.0-21.0), respectively. Total manual muscle test (MMT) scores decreased annually in patients with DMD, IMD, and BMD. Overall, when age increased by 1 year, total MMT scores decreased on average by -1.978, -1.681, and -1.303 in patients with DMD (p<0.001), IMD (p<0.001), and BMD (p<0.001), respectively. Exonic deletion and duplication were reported in 147 (67%) and 31 (14%) of the 218 unrelated probands, respectively. A total of 37 different small sequence variants were found in 40 (18%) of the 218 probands. The reading frame rule was applicable to 142 (94%) of the 151 probands. The present results highlight the long-term natural history and genetic spectrum of dystrophinopathy in a large-scale Korean cohort.

Precise Pulmonary Function Evaluation and Management of a Patient With Freeman-Sheldon Syndrome Associated With Recurrent Pneumonia and Chronic Respiratory Insufficiency.

Freeman-Sheldon syndrome (FSS) is a rare distal arthrogryposis syndrome. There are few reports on the respiratory insufficiency of FSS. Additionally, there is no detailed information on pulmonary functional evaluation. A 17-year-old male patient with FSS developed respiratory failure, leading him to be admitted to hospital several times for evaluation and treatment. Of those times he was admitted, two were due to pneumonia. His pulmonary functions were indicative of a restrictive lung disease potentially caused by severe scoliosis. After a non-invasive ventilatorwas applied correctly to the patient, pulmonary hypertension was normalized. His pulmonary function has been maintained for 13 years. Since receiving proper respiratory care, which includes assisted coughing methods, the patient has not developed pneumonia. It is important to properly evaluate the pulmonary function of patients who have FSS and scoliosis to eliminate the risk of long-term respiratory complications.

Relationship between Eating and Digestive Symptoms and Respiratory Function in Advanced Duchenne Muscular Dystrophy Patients.

BACKGROUND: Duchenne muscular dystrophy (DMD) patients can have various issues that affect their quality of life, including eating and digestive conditions. OBJECTIVE: We sought to identify the relationship between respiratory function and various eating and digestion related symptoms in patients with advanced Duchenne muscular dystrophy (DMD). METHODS: Eating and digestive symptoms, including loss of appetite, nausea, vomiting, diarrhea, constipation, swallowing difficulty, mastication difficulty, early satiety, and aspiration, were evaluated among patients with advanced DMD who were nonambulatory and required noninvasive mechanical ventilatory support. In addition, various respiratory function parameters were measured, including forced vital capacity (FVC), maximal insufflation capacity (MIC), peak cough flow (PCF), assisted PCF (APCF), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). We then analyzed the relationship between gastrointestinal symptoms and respiratory function parameters. RESULTS: A total of 180 patients (age, 22.3±5.0 years) were included in the analysis. Loss of appetite and early satiety showed no correlation with any of the respiratory function parameters. Constipation was correlated with MEP; swallowing difficulty was correlated with MIC, APCF, MIP and MEP; and mastication difficulty was correlated with FVC, PCF, APCF, MIP, and MEP. Notably, age did not correlate with any gastrointestinal symptoms. CONCLUSIONS: Eating and digestive symptoms are more closely correlated with respiratory function than with age in patients with DMD. We think this correlation is mainly caused by the skeletal muscle strength, which is major determinant of both digestive and respiratory function.