Mechanisms of exercise limitation and pulmonary rehabilitation for patients with neuromuscular disease.

Indications for exercise and pulmonary rehabilitation extend to neuromuscular diseases tough these conditions pose particular challenges given the associated skeletal muscle impairment and respiratory muscle dysfunction. These challenges are compounded by the variety of exercise prescriptions (aerobic, muscle strengthening, and respiratory muscle training) and the variety of neuromuscular disorders (muscular, motor neuron, motor nerve root, and neuromuscular transmission disorders). Studies support a level II evidence of effectiveness (i.e., likely to be effective) for a combination of aerobic exercise and strengthening exercises in muscular disorders, and for strengthening exercises in amyotrophic lateral sclerosis. The potential deleterious effects of work overload in the dystrophinopathies have not been confirmed in Becker muscular dystrophy. Adjunctive pharmacologic interventions (e.g., theophylline, steroids, PDE5 inhibitors, creatine), training recommendations (e.g., interval or lower intensity training) and supportive techniques (e.g., noninvasive ventilation, neuromuscular electrical stimulation, and diaphragm pacing) may result in more effective training but require more study before formal recommendations can be made. The exercise prescription should include avoidance of inspiratory muscle training in hypercapnia or low vital capacity, and should match the desired outcome (e.g., extremity training for task-specific performance, exercise training to enhance exercise performance, respiratory muscle training where respiratory muscle involvement contributes to the impairment).

The use of clinical prediction formulas in the evaluation of obstructive sleep apnea.

STUDY OBJECTIVES: To prospectively study the utility of four clinical prediction models for either predicting the presence of obstructive sleep apnea (OSA, apnea-hypopnea index [AHI] > or = 10/hour), or prioritizing patients for a split-night protocol (AHI(3)20/hour). DESIGN: All patients presenting for OSA evaluation completed a research questionnaire that included questions from previously developed clinical prediction models. The probability of sleep apnea for each patient for each model was calculated based upon the equation used in the model. Based upon two cutoffs of apnea-hypopnea index, 10 and 20, the sensitivity, specificity, and positive predictive value were calculated. For the cutoffs AHI > or =10 and > or =20, receiver operating characteristic curves were generated and the areas under the curves calculated. Comparisons of demographic information and symptom response were compared between patients with and without OSA, and men vs. women. SETTING: Urban, accredited sleep disorders center. PATIENTS OR PARTICIPANTS: All patients referred for evaluation of OSA who underwent polysomnography. INTERVENTIONS: N/A. RESULTS: 370 patients (191 men, 179 women) completed the study. 248 of the 370 (67%) patients had an AHI(3)10; 180 of the 370 (49%) had an AHI> or =20. For AHI > or =10, the sensitivities ranged from 76 to 96%, specificities from 13%-54%, positive predictive values from 69%-77% using the probability cutoff of the original investigators; the areas under the curve from 0.669 to 0.736. For AHI(3)20, the areas under the ROC curves ranged from 0.700 to 0.757; using cutoffs to maximized specificity, the sensitivities ranged from 33%-39%, specificities from 87%-93%, and positive predictive values from 72%-85%. All the models performed better for men. CONCLUSIONS: The clinical prediction models tested are not be sufficiently accurate to discriminate between patients with or without OSA but could be useful in prioritizing patients for split-night polysomnography.

Dynamic pharyngoscopy in predicting outcome of uvulopalatopharyngoplasty for moderate and severe obstructive sleep apnea.

STUDY OBJECTIVE: We sought to determine whether preoperative fiberoptic pharyngoscopy (FOP) with Müller's maneuver (dynamic FOP) could be used to establish a subgroup of obstructive sleep apnea (OSA) patients with better outcome after uvulopalatopharyngoplasty (UPPP). DESIGN: Retrospective review of an observational cohort. SETTING: Tertiary care referral center. PATIENTS: Twenty-nine patients who underwent UPPP and nasopharyngeal surgery by one surgeon. INTERVENTION: The patients were divided into two groups based on the findings of preoperative dynamic FOP: group 1 (11 patients) had collapse of the velopharynx and the base of the tongue-epiglottis-hypopharynx (TEH) complex and group 2 (18 patients) had velopharyngeal collapse only. MEASUREMENTS AND RESULTS: Surgical success was defined using a conventional definition (> 50% reduction in the apnea-plus-hypopnea index [OAHI]), and a criterion for cure (> 90% reduction in OAHI and postoperative OAHI < 15). Both groups had a significant improvement in their OAHI. The success rate was significantly higher in patients with velopharyngeal collapse only compared with patients with additional collapse of the TEH complex (78 vs 36% with the conventional definition, and 50 vs 9% using the definition for cure, respectively). Predictive value of dynamic FOP in predicting cure failure when collapse of the TEH complex was present was 91%. CONCLUSIONS: Dynamic FOP may help establish a subgroup of OSA patients with greater likelihood of successful UPPP. The high negative predictive value of dynamic FOP when a criterion for cure is used suggests that this maneuver could best be used to exclude patients with TEH complex collapse from UPPP.

Diagnosis and management of upper airway obstruction.

Upper airway obstruction is a potentially fatal condition that requires prompt diagnosis and treatment. Common causes include foreign body aspiration, infections (even in the adult population) and sequelae of intubation, tracheostomy, and transtracheal oxygen catheters. Spirometry is an insensitive test for diagnosing upper airway obstruction and reflects the functional, rather than anatomic, severity of an obstruction. Although simple tomography still plays an important role, CT and magnetic resonance imaging scans are useful additions to our diagnostic armamentarium. Advances in laser technology, surgery, and bronchoscopy have broadened treatment options but require further evaluation.

Acute exacerbations of chronic bronchitis: focusing management for optimum results.

Acute exacerbations of chronic bronchitis can be recognized clinically by (1) increased cough and dyspnea, (2) a change in character of sputum, and (3) an increase in quantity of sputum. Routine chest radiographs are probably not warranted in initial evaluation. Therapy is aimed at control of inflammation, infection, bronchoconstriction, and mucin production. Corticosteroids improve flow rates in patient with respiratory insufficiency. Antibiotic therapy appears to decrease hospital stay and improve flow rates in patients with bacterial infection, as determined by sputum examination or the presence of two of the following symptoms: increased dyspnea, increased sputum production, purulent sputum. Gram's stain of expectorated sputum often allows targeted and cost-effective therapy. Ipratropium bromide (Atrovent) is the bronchodilator of choice; concomitant use of beta agonists has additional benefit. Research on future therapy may focus on the role of corticosteroids, mucolytic agents, and drugs that counteract the effects of neutrophil elastase. Smoking cessation is the first step in prevention. Antibiotic prophylaxis is warranted only in patients with four or more exacerbations per year. Pneumoccoccal and influenza vaccinations are effective and safe; unfortunately, they are underutilized at present.

Obstructive sleep apnea. Warding off the sometimes dire consequences.

Obstructive sleep apnea (occlusion of the upper airway despite continued respiratory muscle activity) is accompanied by increased morbidity and mortality from cardiovascular and cerebrovascular disease. Daytime sleepiness due to the disorder may also be a factor in a higher incidence of automobile accidents in these patients. An overnight polysomnogram is used to confirm the diagnosis and assess severity of physiologic disturbances. Initially, simple measures, such as avoidance of alcohol and sedatives before bedtime and sleeping on the side rather than the back, may be tried. Nasal continuous positive airway pressure is considered first-line therapy, and compliance can be improved by education and counseling of the patient. Uvulopalatopharyngoplasty is beneficial in only 50% of patients. Tracheostomy gives the most consistent long-term benefit but is accompanied by significant emotional morbidity.

Fever and Cough in Methotrexate-treated Patients: An Approach.

The prevalence of acute methotrexate pneumonitis is up to 5.5%. Its presentation is often difficult to distinguish from opportunistic infections such as Pneumocystis carinii, nocardia, and cryptococcus or from interstitial infiltrates from the underlying rheumatic disease. Its recognition rests on the presence of cough, dyspnea, fever, new pulmonary function test abnormalities, and acute infiltrates on chest radiograph. The diagnosis ultimately rests on histologic confirmation and exclusion of infection. Bronchoalveolar lavage for cultures, and special staining of lavage and transbronchial histopathology specimens, often allows identification of opportunistic pathogens. Transbronchial biopsy may provide sufficient material for the diagnosis of either methotrexate pneumonitis of rheumatoid lung, particularly when correlated with the clinical presentation. Open lung biopsy should be considered if a diagnosis cannot be obtained on bronchoscopy. Despite a mortality of up to 10%, methotrexate pneumonitis usually responds to discontinuation of the drug and trial of corticosteroids.

The hepatopulmonary syndrome.

The hepatopulmonary syndrome is a triad of liver disease, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilatations. Manifestations include orthodeoxia, platypnoea and hyperdynamic circulation. Intrapulmonary vascular abnormalities, perhaps mediated by nitric oxide, cause hypoxaemia by shunting, a perfusion-diffusion defect, and ventilation-perfusion mismatching. Contrast-enhanced echocardiography is the method of choice for demonstrating pulmonary vascular abnormalities, although perfusion lung scanning is a more specific and sensitive test. Angiography is best reserved for patients with poor response to 100% oxygen and defines whether vascular dilatations are of the diffuse 'spongy' type or, less commonly, discrete arteriovenous communications amenable to embolization. About 80% of patients with the hepatopulmonary syndrome eventually have improved oxygenation after liver transplantation, thereby making worsening hypoxaemia the primary indication for transplantation in many instances. Nevertheless, severe hypoxaemia carries a peri-operative mortality of 30% and reliable predictors of successful outcome after transplantation remain to be determined.

alpha1-Antitrypsin deficiency . 5: intravenous augmentation therapy: current understanding.

The biochemical and clinical efficacy of intravenous augmentation therapy in alpha(1)-antitrypsin deficiency is reviewed, adverse events experienced with this treatment are considered, and its cost effectiveness is discussed.

Effect of noninvasive positive-pressure ventilation on survival in amyotrophic lateral sclerosis.

BACKGROUND: Noninvasive positive-pressure ventilation may benefit patients with amyotrophic lateral sclerosis and respiratory insufficiency. OBJECTIVE: To determine 1) whether patients tolerant of noninvasive positive-pressure ventilation have better survival than intolerant patients and 2) whether bulbar symptoms account for intolerance of noninvasive positive-pressure ventilation. DESIGN: Observational cohort study. SETTING: Tertiary care referral center. PATIENTS: 39 patients with amyotrophic lateral sclerosis who were treated with noninvasive positive-pressure ventilation. INTERVENTION: Noninvasive positive-pressure ventilation was started for patients with new orthopnea, new hypercapnia, or both. Patients were divided into two groups: those tolerant of and those intolerant of noninvasive positive-pressure ventilation. RESULTS: The risk for death from onset of respiratory insufficiency was higher for intolerant patients than for tolerant patients (relative risk, 3.1 [95% CI, 1.8 to 9.6]). Moderate or severe bulbar symptoms were more prevalent among intolerant patients than among tolerant patients (67% compared with 33%; P = 0.04). CONCLUSIONS: Among patients with amyotrophic lateral sclerosis, those who are tolerant of noninvasive positive-pressure ventilation have better survival than do those who are intolerant. Bulbar symptoms partially account for intolerance of noninvasive positive-pressure ventilation.

Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis.

The impact of noninvasive positive-pressure ventilation (NIPPV) on pulmonary function studies, quality of life, and survival was assessed in patients with amyotrophic lateral sclerosis. NIPPV did not change the rate of decline of the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)) (2.31 and 2.09 percent-predicted points per month, respectively). NIPPV resulted in a drop of FEV(1) by 5.94 percent-predicted points (P = 0.07), and of maximal inspiratory pressure by 6.33 percent-predicted points (P = 0.11). The change in FEV(1) and FVC pre- and postintervention correlated with the corresponding change in maximal inspiratory pressure. Fatigue and mastery scores were improved by NIPPV. Median survivals in patients intolerant and tolerant of NIPPV were 5 and 20 months, respectively (P = 0.002). Although NIPPV has no impact on the rate of decline of lung function and may have deleterious effects on spirometric measures, it may improve quality of life and survival.

Hypoplastic trachea in Down's syndrome.

Our study sought to determine whether tracheal dimensions were reduced in patients with Down's syndrome and whether such a narrowing, if present, was related to the presence of congenital heart disease or to body habitus (height or weight). The inner diameter of the tracheal air column was measured at 2 cm above the aortic arch in 14 adult patients with Down's syndrome, and the results compared with previously established norms. Two-way analysis of variance showed no significant difference in z-scores between sexes or between those with or without congenital heart disease. Z-scores were significantly different from zero for both coronal diameters (p = 0.0010) and sagittal diameters (p = 0.0003). The negative limits on the 95% confidence interval for coronal z-scores (-2.5 to -0.8) and sagittal z-scores (-2.6 to -1.0) indicate that our patients have tracheal diameters significantly smaller than normal. Linear regression analysis showed no significant correlation between tracheal diameters and patients' height or weight. We conclude that tracheal diameters in adult patients with Down's syndrome are reduced and that the narrowing cannot be ascribed to associated congenital heart disease or to body habitus.