Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Riluzole is a drug used in the treatment of amyotrophic lateral sclerosis. To date, reports of lung toxicity have been exceptional. We present the case of a 74-year-old man diagnosed with amyotrophic lateral sclerosis. Following 3, 5 months of treatment with riluzole (Rilutek), the patient began to present a clinical picture consisting of nonproductive cough, progressive dyspnea (even with slight exertion), weakness, and radiologic progression with the appearance of predominantly peripheral bilateral pulmonary infiltrates that did not respond to treatment with amoxicillin-clavulanic acid. Bacterial tests did not reveal the presence of germs, nor did other examinations suggest an alternative diagnosis. The patient did not resume treatment with the drug or undergo complementary procedures aimed at obtaining histologic samples. Nevertheless, the coincidence in time, lack of response to antibiotic treatment, remission of symptoms following withdrawal of the drug without initiating any other treatment except 40 mg/d of methylprednisolone for 6 days, absence of alternative diagnoses, and suggestive clinical and radiologic findings all together point to toxicity due to riluzole.
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PMID:[Strong suspicion of lung toxicity due to riluzole]. 1642 23

Pseudobulbar affect (PBA), a condition involving involuntary and uncontrollable episodes of crying and/or laughing, occurs frequently in patients with a variety of neurological disorders, including amyotrophic lateral sclerosis (ALS), stroke, traumatic brain injury, dementia including Alzheimer's disease, and multiple sclerosis (MS). Although PBA results in considerable distress for patients and caretakers, it is underrecognized and undertreated. Agents used to treat psychiatric disorders--particularly tricyclic antidepressants and selective serotonin reuptake inhibitors--are useful in alleviating PBA, but act on diffuse neural networks rather than targeting those involved in emotional motor expression. As a result of their nonspecific activity, these agents are associated with a range of unwanted effects that preclude many patients from using them. Dextromethorphan, a common cough suppressant, specifically targets sigma(1) receptors concentrated in the brainstem and cerebellum, thus providing the possibility of targeting regions implicated in emotional expression. When administered in a fixed combination with quinidine, dextromethorphan is effective in treating PBA in patients with ALS, and preliminary results suggest that this therapy also is effective in treating MS-related PBA.
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PMID:Pseudobulbar affect in multiple sclerosis: toward the development of innovative therapeutic strategies. 1667 78

Respiratory complications are common in patients with amyotrophic lateral sclerosis (ALS) with respiratory failure representing the most common cause of death. Ineffective airway clearance resultant from deficient cough frequently contributes to these abnormalities. We sought to evaluate the effectiveness of high frequency chest wall oscillation (HFCWO) administered through the Vest Airway Clearance System when added to standard care in preventing pulmonary complications and prolonging the time to death in patients with ALS. This is a single center study performed at the Penn State Milton S. Hershey Medical Center (HMC). Nine patients with a diagnosis of ALS and concurrently receiving non-invasive ventilatory support with bi-level positive airway pressure (BiPAP) were recruited from the outpatient clinic at HMC. Four patients were randomized to receive standard care and five patients to receive standard care plus the addition of HFCWO administered twice-daily for 15 min duration. Longitudinal assessments of oxyhemoglobin saturation, forced vital capacity (FVC), and adverse events were obtained until time of death. Pulmonary complications of atelectasis, pneumonia, hospitalization for a respiratory-related abnormality, and tracheostomy with mechanical ventilation were monitored throughout the study duration. No differences were observed between treatment groups in relation to the rate of decline in FVC. The addition of HFCWO airway clearance failed to improve time to death compared to standard treatment alone (340 days +/- 247 vs. 470 days +/- 241; p = 0.26). The random allocation of HFCWO airway clearance to patients with ALS concomitantly receiving BiPAP failed to attain any significant clinical benefits in relation to either loss of lung function or mortality. This study does not exclude the potential benefit of HFCWO in select patients with ALS who have coexistent pulmonary diseases, pre-existent mucus-related pulmonary complications, or less severe levels of respiratory muscle weakness.
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PMID:A clinical pilot study: high frequency chest wall oscillation airway clearance in patients with amyotrophic lateral sclerosis. 1675 75

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. No treatment is currently able to stop the disease process. In the absence of new active compounds there is an urgent need to develop new strategies based on the neuroprotective activity of available drugs. ALS is a heterogeneous disease. To build up these therapeutic trials, we need to have a better understanding of the prognostic factors in this disease. During the Phase IV Rilutek Trial in France, we developed in a large population of patients a prognostic score based on clinical parameters available at the bedside. The most significant variables are vital capacity, spasticity, fasciculations, swallowing, cough and creatininemia. This score proved to be very useful in daily use in the clinic and for planning disease management in ALS as in the design of therapeutic trials. In ALS clinical trials, efficacy can be evaluated using survival or functional parameters. In phase II trials, function remains the most commonly used. In phase III trials, the gold standard endpoint remains the survival rate at month 18. We analyzed the most recent ALS trials published in the literature. This review suggests that in these trials there is a discrepancy between drug effects on survival versus function. These results suggest that a reappraisal of strategies to identify therapeutic targets for ALS is required.
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PMID:Clinical trials in ALS: what did we learn from recent trials in humans? 1690 27

Although noninvasive ventilation may improve survival in patients with amyotrophic lateral sclerosis (ALS), ineffective airway clearance is an important cause of therapeutic failure. We report in this paper the main studies which have assessed assisted cough techniques in patients with ALS. Manually assisted cough (in particular with previous air stacking) and mechanical insufflation/exsufflation may significantly increase cough peak flow. Characteristics, limitations and long-term benefits of these techniques are also discussed.
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PMID:[Techniques favoring airway clearance in patients with amyotrophic lateral sclerosis]. 1712 20

The impact of ventilatory support on the natural history of neuromuscular disease (NMD) has become clearer over the last 2 decades as techniques have been more widely applied. Noninvasive ventilation (NIV) allows some patients with nonprogressive pathology to live to nearly normal life expectancy, extends survival by many years in patients with other conditions (eg, Duchenne muscular dystrophy), and in those patients with rapidly deteriorating disease (eg, amyotrophic lateral sclerosis) survival may be increased, but symptoms can be palliated even if mortality is not reduced. A growing number of children with NMD are surviving to adulthood with the aid of ventilatory support. The combination of NIV with cough-assist techniques decreases pulmonary morbidity and hospital admissions. Trials have confirmed that NIV works in part by enhancing chemosensitivity, and in patients with many different neuromuscular conditions the most effective time to introduce NIV is when symptomatic sleep-disordered breathing develops.
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PMID:Recent advances in respiratory care for neuromuscular disease. 1716 12

A variety of neurological conditions and disease states are accompanied by pseudobulbar affect (PBA), an emotional disorder characterized by uncontrollable outbursts of laughing and crying. The causes of PBA are unclear but may involve lesions in neural circuits regulating the motor output of emotional expression. Several agents used in treating other psychiatric disorders have been applied in the treatment of PBA with some success but data are limited and these agents are associated with unpleasant side effects due to nonspecific activity in diffuse neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at receptors in the brainstem and cerebellum, brain regions implicated in the regulation of emotional output. The combination of DM and quinidine (Q), an enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III clinical trials in patients with multiple sclerosis and amyotrophic lateral sclerosis and was both safe and effective in palliating PBA symptoms. In addition, clinical studies pertaining to the safety and efficacy of DM/Q in a variety of neurological disease states are ongoing.
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PMID:Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar affect. 1743 20

In home respiratory management, an important issue to consider is for patients at home with neuromuscular diseases. Under the current condition, however, a technical support is not offered sufficiently. In evaluating the effect of respiratory physical therapy, we have found significant differences in both between peak cough flow (PCF) and assisted peak cough flow (a-PCF) and between vital capacity (VC) and maximum inspiratory capacity (MIC) for patients with spontaneous ventilation and those with non-invasive positive pressure ventilation (NPPV). Since in neuromuscular diseases, it is not rare that the patients fall into acute respiratory insufficiency due to the difficulty of sputum expectoration, the respiratory physical therapy to strengthen the ability of coughing is considered useful. In the case of rapidly worsening amyotrophic lateral sclerosis (ALS), the effect of this therapy lasts only briefly, but it is considered necessary to popularize this technique, because neuromuscular diseases require a different approach in respiratory physical therapy, compared to other pulmonary diseases such as chronic obstructive pulmonary diseases.
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PMID:[Home respiratory management--an attempt at respiratory physical therapy for neuromuscular diseases]. 1746 49

Assessing and monitoring respiratory muscle function is crucial in patients with Amyotrophic Lateral Sclerosis, since impaired function can lead to either ventilatory failure or respiratory tract infection. Spirometry, diffusing capacity of the lung, breathing pattern, sleep study, blood gas analysis and respiratory muscle strength tests, as well as cough peak flow and cough expiratory volume measurements can provide relevant information on ventilatory function and cough efficacy. With regard to respiratory muscle strength testing, the rational approach consists in starting with volitional and non-invasive tests and later using invasive and non-volitional tests. This review focuses on both ventilatory and respiratory muscle strength testing, in order to undertake a timely treatment of respiratory failure and/or impaired cough efficacy. So far, the current literature has not highlighted any gold standard which stipulates when to commence ventilation and cough support in patients with Amyotrophic Lateral Sclerosis. A composite set of clinical and functional parameters is required for treatment scheduling to monitor lung involvement and follow-up in these patients.
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PMID:Assessment and monitoring of ventilatory function and cough efficacy in patients with amyotrophic lateral sclerosis. 1756 84

Neuromuscular diseases affect alveolar air exchange and therefore cause chronic respiratory failure. The onset of respiratory failure can be acute, as in traumas, or progressive (slow or rapid), as in amyotrophic lateral sclerosis, muscular dystrophies, diseases of the myoneural junction, etc. Respiratory muscle impairment also affects cough efficiency and, according to the current knowledge regarding the type of treatment available in Brazil to these patients, it can be said that the high rates of morbidity and mortality in these individuals are more often related to the fact that they cough inefficiently rather than to the fact that they ventilate poorly. In this review, with the objective of presenting the options of devices available to support and substitute for natural ventilation in patients with neuromuscular diseases, we have compiled a brief history of the evolution of orthopedic braces and prostheses used to aid respiration since the end of the 19th century. In addition, we highlight the elements that are fundamental to the diagnosis of alveolar hypoventilation and of failure of the protective cough mechanism: taking of a clinical history; determination of peak cough flow; measurement of maximal inspiratory and expiratory pressures; spirometry in two positions (sitting and supine); pulse oximetry; capnography; and polysomnography. Furthermore, the threshold values available in the literature for the use of nocturnal ventilatory support and for the extension of this support through the daytime period are presented. Moreover, the maneuvers used to increase cough efficiency, as well as the proper timing of their introduction, are discussed.
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PMID:Chronic respiratory failure in patients with neuromuscular diseases: diagnosis and treatment. 1756 73


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