Plasma Krebs von den Lungen glycoprotein, lung injury, and noninvasive ventilation in Duchenne muscular dystrophy.

OBJECTIVE: There have been few reports of ventilator-induced lung injury associated with noninvasive ventilation (NIV), but many with invasive mechanical ventilation. The purpose of this study was to detect subclinical NIV-associated lung injury by monitoring Krebs von den Lungen glycoprotein plasma levels. DESIGN: Forty-one Duchenne muscular dystrophy patients were divided into three categories: group 1, asymptomatic and not using ventilators; group 2, NIV use less than 24 hrs/day at full ventilatory support settings; and group 3, continuous NIV dependence. Plasma Krebs von den Lungen glycoprotein level was measured by electrochemical luminescent immunoassay using Krebs von den Lungen glycoprotein antibodies. One-way analysis of variance, followed by the Tukey-Kramer test, was used as appropriate to compare intergroup differences. RESULTS: Extent of ventilator dependence correlated with age (P < 0.05). Intergroup plasma Krebs von den Lungen glycoprotein levels were not significantly different. CONCLUSIONS: NIV used at volumes and pressures of full (invasive) ventilatory support may not induce the alveolar septal barrier injury commonly seen with invasive mechanical ventilation.

Indicators for ventilator use in Duchenne muscular dystrophy.

BACKGROUND: Noninvasive mechanical ventilation is being used up to continuously by patients with Duchenne muscular dystrophy (DMD). Invasive and noninvasive tests are used to assess ventilatory function but there are few reports relating them to extent of ventilator dependence for which simple and cost effective parameters are needed. OBJECTIVE: To investigate the relative efficacy of noninvasive lung function parameters for determining extent of need for ventilator use. MATERIALS AND METHODS: 83 DMD patients were divided into three groups: no ventilator use (asymptomatic) (n = 26) [Group 1], nocturnal ventilator use (symptomatic) (n = 20) [Group 2], and full-time ventilator dependence (n = 37) [Group 3]. Tidal volume (TV), vital capacity (VC), respiratory rate (RR), inspiratory time (Ti), respiratory cycle time (Ttot), rapid shallow breathing index (RSBI [RR/TV]), breathing intolerance index (BITI), ventilator requirement index (VRI) and a new parameter RR/VC were monitored and compared. Data were analyzed with receiver-operating-characteristic curves (ROC) and the area under the curve (AUC) was calculated. RESULTS: In group 2 and 3, patients used NIV for 3.3 ± 2.1 and 11.2 ± 4.7 years, respectively. By ROC comparison, RR/VC (RR/VC ≥ 0.024 [AUC, 0.921] and ≥0.071 [AUC, 0.935]), RR/TV (RR/TV ≥ 0.024 [AUC, 0.905] and ≥0.153 [AUC, 0.905]), and VC (VC ≤ 770 ml [AUC, 0.896] and ≤370 ml [AUC, 0.898]) represented to introduce nocturnal and continuous ventilator use, respectively. TV/VC, BITI, and VRI were either less sensitive or less specific. CONCLUSIONS: Lung function parameters including RR/VC, RR/TV, and VC are useful and inexpensive in predicting the extent of need for ventilator use. Overall, RR/VC is the most appropriate predictor for determining extent of need for ventilator use.

Duchenne muscular dystrophy: survival by cardio-respiratory interventions.

We describe survival in Duchenne dystrophy by invasive and noninvasive ventilation vs. untreated. Patients were untreated prior to 1984 (Group 1), underwent tracheotomy from 1984 until 1991 (Group 2), and were managed by noninvasive mechanical ventilation and cardioprotective medications subsequently (Group 3). Symptoms, vital capacity, and blood gases were monitored for all and spirometry, cough peak flows, carbon dioxide tension, and oximetry for Group 3. Sleep nasal ventilation was initiated for symptomatic hypoventilation. An oximeter and mechanical cough assistance were prescribed for maximum assisted cough peak flow <300 L/m. Patients used continuous noninvasive ventilation and mechanically assisted coughing as needed to maintain pulse oxyhemoglobin saturation ≥95%. Survival was compared by Kaplan-Meier analysis. The 56 of Group 1 died at 18.6±2.9, the 21 Group 2 at 28.1±8.3 years of age with three still alive, and the 88 using noninvasive ventilation had 50% survival to 39.6 years, p<0.001, respectively. We conclude that noninvasive mechanical ventilation and assisted coughing provided by specifically trained physicians and therapists, and cardioprotective medication can result in more favorable outcomes and better survival by comparison with invasive treatment.

Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) often have severe heart failure with a high mortality rate. Most DMD patients with cardiomyopathy became symptomatic in their early to middle teens and usually die of congestive heart failure within 2-3 years from the onset of symptoms. It has been reported that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker has additive benefits in patients with heart failure. The aim of this study was to assess whether the combination of an ACE inhibitor and a beta-blocker is associated with long-term survival of DMD patients with left ventricular (LV) dysfunction. METHODS: We retrospectively analyzed the outcomes of 52 DMD patients who had begun treatment for heart failure with an ACE inhibitor and a beta-blocker at National Yakumo Hospital during the period from 1992 to 2005. All patients used wheelchairs in their daily lives. Patients were classified as symptomatic or asymptomatic at the initiation of treatment with these two drugs. Twelve patients who had already had apparent symptoms due to heart failure were enrolled in a treatment group. Forty patients who had no symptoms with reduced LV ejection fraction (≤ 45% in echocardiography) were enrolled in a prevention group. RESULTS: Five-year and 7-year survival rates of all patients were 93 and 84%, respectively. In the treatment group, 5-year and 7-year survival rate were 81 and 71%, respectively. Survival rate became zero at 10.9 years. In the prevention group, 5-year and 7-year survival rates were 97 and 84%, respectively, and 10-year survival rate was 72%. Nine patients in the prevention group remained event-free over 10 years. CONCLUSIONS: In this study, the combination of an ACE inhibitor and a beta-blocker had a beneficial effect on long-term survival of DMD patients with heart failure. The treatment was particularly effective for asymptomatic patients with LV dysfunction.

Myocardial strain changes in Duchenne muscular dystrophy without overt cardiomyopathy.

BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) are at risk of the development of dilated cardiomyopathy and heart failure, thus making early identification of high-risk patients necessary. Myocardial strain imaging (MSI) can be used for quantitative analysis of wall motion of the left ventricle (LV). The aim of this study was to determine whether MSI could detect early changes in myocardial properties in presymptomatic DMD patients with normal LV function. METHODS AND RESULTS: Two-dimensional echocardiographic and tissue Doppler examinations were performed in 13 DMD patients (age range, 11 to 20 years) with normal LV function and in 10 healthy controls. MSI was obtained from tissue Doppler information. In control subjects, strain values in both inner and outer layers of the myocardium were positive at the short-axis image showing the radial systolic thickening. In 10 of the 13 DMD patients, however, myocardial strain showed a negative strain value in systole in the outer layer of the posterolateral wall at the parasternal short-axis image for each cardiac cycle. In 5 of these 10 patients, the timing of the peak systolic velocity at the inferoposterior wall was delayed more than 60 ms than that at the posterolateral wall (mean 80.0+/-17.5 ms). CONCLUSIONS: In some DMD patients with normal LV function, myocardial strain profiles at the posterolateral wall of the LV were different from those in healthy controls, suggesting abnormal myocardial contraction. MSI appears to detect early changes in myocardial features in DMD patients before the onset of overt cardiomyopathy.

[Changes in the clinical picture of Fukuyama type. Congenital muscular dystrophy in its advanced stage: effectiveness of mechanical ventilation systems].

We studied the clinical courses of Fukuyama type congenital muscular dystrophy (FCMD) based on a long-term follow-up of 7 patients. Their peak motor function varied from controlling the head incompletely to standing with support. Six patients had epilepsy, which in some cases was diagnosed with difficulty because of changing seizure types and multiple joint contracture. Six patients underwent endotracheal intubation, and in 5 of them long-term mechanical ventilation began at the age of 15 to 20 years. Three of them underwent trachestomy intermittent positive pressure ventilation (TIPPV), whereas recently 2 patients were treated successfully with nasal intermittent positive pressure ventilation (NIPPV). Mechanical in-exsufflation (MI-E) was effective in clearing airway secretion of 4 patients. With disease progression, the motor, mental, nutritional, cardiorespiratory and swallowing functions of FCMD patients should be assessed to ensure adequate management by NIPPV and MI-E.