Cough In Patients Research Articles

The Association of Obesity, Airway Hyperresponsiveness and Atopy in Chronic Cough Patients: Results of a Two-Center Study

1 , Jong Won Park, M.D. Background: The rising prevalence of asthma worldwide may be associated with the rising prevalence of obesity in developed nations. Although several studies have suggested a relationship between asthma and obesity, controversy still remains. The aim of this study was to examine the relationship between obesity and asthmatic factors such as atopy, eosinophilia, serum total Ig E and bronchial hyperresponsiveness in chronic cough patients. Methods: This study was a retrospective, observational study in two centers done between January 2007 and June 2008. The subjects included individuals who had a chronic cough. We examined body mass index (BMI) to measure obesity and pulmonary function. We did a metacholine provocation test for airway hyperresponsiveness (AHR), a skin prick test for atopy, and tests for blood eosinophils and serum IgE. Results: A total of 1022 subjects were included. Airway hyperresponsiveness was not related with obesity (p=0.06), and atopy incidence was significant higher in non obese patients (p=0.00). There was no significant difference in serum IgE and blood eosinophil counts between obese and non obese patients. Forced expiratory volue in one second (FEV 1)/forced vital capacity (FVC) was significantly reduced in obese patients (p=0.03), but FEV1 and FVC were no significant difference between obese and non obese patients. Conclusion: There is no relationship between obesity and bronchial hyperresponsiveness. The nonobese group appears to have more atopy. The relationship between obesity and bronchial hyperresponsiveness and atopy need further investigation.

S119 Variation in pharyngeal pH in the diagnosis of airway reflux

Introduction and objectivesReflux of gastric contents to the laryngopharynx has been implicated in the pathogenesis of chronic cough and may exacerbate other respiratory conditions. Direct measurement of pharyngeal pH is...

S116 Urge-to-cough intensity in chronic cough patients compared to asthmatics and healthy controls

BackgroundHealthy subjects inhaling increasing doses of capsaicin perceive an urge-to-cough (UTC) prior to initiating coughing. We compared subjective ratings of UTC intensity following inhalation of capsaicin in patients with chronic...

New insights in cough

Chronic cough is common, blights patients' lives and is hard to treat. Chronic cough patients demonstrate high objective cough rates and as a group have increased cough reflex sensitivity. However, conventional cough challenge techniques show substantial overlap with normal subjects. This suggests that other important mechanisms have yet to be determined. For the last two decades, chronic cough has been considered to be caused by gastro-oesophageal reflux, post-nasal drip or asthma. However, many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. In addition, many chronic cough patients do not have an identifiable cause. This raises questions about the concept of a triad of treatable causes for chronic cough. Our current understanding of the neurophysiology of the cough reflex is largely derived from animal work with limited data in humans. By analogy with chronic pain syndromes, both peripheral and central sensitization may be important mechanisms in chronic cough, and are under active investigation. We need to understand the mechanisms underlying sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Only then will we develop effective interventions.

GERD-related Chronic Cough

GERD-related Chronic Cough

Chronic cough and obstructive sleep apnea in a community-based pulmonary practice.

BackgroundRecent reports suggest an association between unexplained chronic cough and obstructive sleep apnea (OSA). Current guidelines provide an empiric integrative approach to the management of chronic cough, particularly for etiologies of gastroesophageal reflux (GERD), upper airway cough syndrome (UACS) and cough variant asthma (CVA) but do not provide any recommendations regarding testing for OSA. This study was done to evaluate the prevalence of OSA in patients referred for chronic cough and examine the impact of treating OSA in resolution of chronic cough.MethodsA retrospective review of chronic cough patients seen over a four-year period in a community-based pulmonary practice was done. Patients with abnormal chest radiographs, abnormal pulmonary function tests, history of known parenchymal lung disease, and inadequate followup were excluded. Clinical data, treatments provided and degree of resolution of cough was evaluated based on chart review. Specifically, diagnostic testing for OSA and impact of management of OSA on chronic cough was assessed.Results75 patients with isolated chronic cough were identified. 44/75 had single etiologies for cough (GERD 37%, UACS 12%, CVA 8%). 31/75 had multiple etiologies for their chronic cough (GERD-UACS 31%, GERD-CVA 5%, UACS-CVA 3%, GERD-UACS-CVA 3%). 31% patients underwent further diagnostic testing to evaluate for UACS, GERD and CVA. Specific testing for OSA was carried out in 38/75 (51%) patients and 33/75 (44%) were found to have obstructive sleep apnea. 93% of the patients that had interventions to optimize their sleep-disordered breathing had improvement in their cough.ConclusionsOSA is a common finding in patients with chronic cough, even when another cause of cough has been identified. CPAP therapy in combination with other specific therapy for cough leads to a reduction in cough severity. Sleep apnea evaluation and therapy needs to considered early during the management of chronic cough and as a part of the diagnostic workup for chronic cough.

Relation between Subjective Symptoms and Rhinolaryngoscopic Findings or Sputum Eosinophilia in Chronic Cough Patients

Background: Rhinolaryngoscopy and sputum examination are popular tests for the evaluation of chronic cough. Little is known about the relationship between symptoms and rhinolaryngoscopic findings or sputum eosinophilia in chronic cough patients. Methods: One hundred patients, who had chronic cough with normal chest radiography and who also had undergone both rhinolaryngoscopy and induced sputum analysis, were reviewed retrospectively. Eleven associated symptoms of chronic cough were asked; postnasal drip (PND) and laryngopharyngeal reflux (LPR) were examined by rhinolaryngoscopy. Induced sputum analysis was performed for evaluation of sputum eosinophilia. Cross tabulation analyses with chi-square tests were used to evaluate the relationship between symptoms and objective findings. Results: The most frequent symptom was sputum (70%). The prevalence of PND and LPR on rhinolaryngoscopy were 56% (56/100) and 25.6% (22/86), respectively. Sputum eosinophilia was observed in 23 (23.7%) of 97 patients. The dyspnea (p=0.001), sputum (p=0.003), nasal obstruction (p=0.023), and postnasal drip sense (p=0.025) were related with PND on rhinolaryngoscopy. LPR on rhinolaryngoscopy was not related with any symptoms. Dyspnea (p=0.003), wheezing (p=0.005), nasal obstruction (p=0.013), and belching (p=0.018) were related with sputum eosinophilia. Conclusion: Any symptoms might not be related with LPR on laryngoscopy. Some symptoms might be related with PND on rhinoscopy or with sputum eosinophilia.

New Developments in Reflux-Associated Cough

Gastro-oesophageal reflux disease (GORD) is generally considered one of the three main causes of chronic cough, along with asthma and nasal disease. The diagnosis of GORD is often based upon a successful trial of anti-acid treatment however GORD is a complex condition taking many forms. Only recently have studies started to address the different types of GORD in patients with chronic cough and how these may infer the mechanisms linking these common conditions. GORD can be assessed in a number of ways; whilst endoscopy provides evidence of oesophagitis (i.e. erosive disease), 24-h ambulatory oesophageal pH monitoring may demonstrate abnormal oesophageal acid exposure in the absence of oesophageal damage (i.e. non-erosive disease). The development of oesophageal impedance monitoring now allows the assessment of all reflux events (regardless of degree of acidity) and further classification of reflux by the proximal extension e.g. to upper oesophagus or even pharynx. Chronic cough patients may still be considered to have GORD if there is a significant temporal association between reflux events and coughing. Recent studies have examined the relationships between cough and reflux events, the roles of distal and proximal/pharyngeal reflux and also micro-aspiration in chronic cough patients. Increasing evidence suggests a significant proportion of patients display statistical associations between reflux and cough events, in the absence of an excessive numbers of reflux events either within or outside of the oesophagus.

이비인후과 영역에서 만성 기침을 유발하는 질환의 분석

Background and Objectives: Cough is one of the most common symptoms for which adult patients seek medical attention. Two diseases of pathologic triad of chronic cough, post-nasal drip syndrome and reflux disease, are categorized into otorhinolaryngologic field. This study is designed to find out possible causes of cough in otorhinolaryngologic field and to inspire the need for scrupulous examination on chronic cough patients. Materials and Methods: All of 554 patients refered to the department of otorhinolaryngology for chronic cough lasting over 3 weeks were reviewed retrospectively. With excluding smokers and patients in whom specific causative disorders had been confirmed at other departments or required surgical management, otorhinolaryngologic causes were evaluated on 123 patients. The presumptive diagnoses were determined from clinical, laboratory and radiological findings. And the final diagnosis was determined from trials of therapeutics. Subjective discomfort induced by cough was measured with visual analogue scale (VAS) and compared before and after treatment. Results: The three most important causative diseases for chronic cough on otorhinolaryngolgic field were chronic rhinosinusitis (60.2%), allergic rhinitis (52.8%) and laryngopharyngeal reflux (39.8%). In 47 patients (38.2%), two or more causes were found. The success rate of treatment was 89.3%. Subjective discomfort on VAS has improved from 6.6 to 1.2 after treatment. Conclusion: This study revealed that 22.2% of chronic cough patients had otorhinolaryngologic causes and most of them could be controlled with proper diagnosis and management. Therefore, otorhinolaryngologists should keep all possible causes for cough in mind and carefully evaluate patients of chronic cough. (J Clinical Otolaryngol 2009;20:229-234)

Prospective Questionnaire-Based Evaluation of the Prevalence of Urinary Incontinence in Women with Chronic Cough

Purpose: Because chronic cough leads to repeated increases in intra-abdominal pressure, it might cause or unmask stress urinary incontinence (SUI). To test this hypothesis, we performed a cross-sectional prospective survey of women with chronic cough and female subjects without cough symptoms. Methods: A group of women with chronic cough (n = 297) presenting at a specialty asthma/allergy clinic over an 18-month period and a control group (n = 106) completed a self-administered survey that included the Urogenital Distress Inventory (UDI)-6 questionnaire and a global quality of life (QOL) question. Subjects on medication for bladder symptoms (n = 14) or who had undergone prior anti-incontinence surgery (n = 29) were excluded. Results: 263 patients and 97 control subjects met criteria for analysis. Chronic cough patients were older than control subjects (median 41 versus 35 years; p < 0.001). There was no difference in weight between groups (p = 0.544). The UDI-6 question responses correlated with each other and with the responses to the QOL questions (p values ≤0.002). Chronic cough patients were more bothered by urinary frequency (UDI question 1, 33 vs. 20%, p = 0.018), sense of incomplete emptying (UDI question 5, 10 vs. 3%, p = 0.047). There was no statistical difference in SUI between chronic cough patients and controls (UDI question 3, 24 vs. 15%, p = 0.059). Conclusions: Based on this exploratory study, we found no statistically significant difference in the prevalence of SUI between patients with or without chronic cough. However, increased urinary frequency may have had a protective effect on SUI, thereby masking a larger difference in SUI.

The etiological distribution of 146 cases of chronic cough patients

Objective To analyze the causes of chronic cough. Results Totally 146 patients with chronic cough were diaguosed according to the diagnostic routine based on the guideline on diagnosis and treatment of chronic cough established by Chinese Medical Association, which included medical history, medical examination, X-ray or CT of paranasal sinus or chest, lung function, gastroscope, sputum cytology classification. The final diagnosis was made based on clinical manifestation examination findings and a positive response to therapy. Conclusion The cause of chronic cough was defined in 93.2% of the patients, and multiple causes: Cough variant asthma (n = 45,30.3%), postnasal drip syndrome,PNDs (n = 27, 18.5%), gastroesophageal reflux cough(n = 21,14.4%), post infection cough(n = 16,10.9%), ensinophilic bronchitis(n = 13, 8.9%), drug induced cough(n = 10,6.8%), unidentified cough(n = 10,6.8%). Conclusion Complex etiology of chronic cough,be specific therapeutic effect,and its clear cause is the key to treatment. Key words: Chronic cough; Cause of disease'

Expression of transforming growth factor-beta (TGF-beta) in chronic idiopathic cough.

In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFβ and neurotrophins.We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies.There was a significant increase in the levels of TGFβ in BAL fluid, but not of nerve growth factor(NGF) and brain-derived nerve growth factor(BDNF) compared to normal volunteers. Levels of TFGβ gene and protein expression were assessed in bronchial biopsies. mRNA expression for TGFβ was observed in laser-captured airway smooth muscle and epithelial cells, and protein expression by immunohistochemistry was increased in ASM cells in chronic cough patients, associated with an increase in nuclear expression of the transcription factor, smad 2/3. Subbasement membrane thickness was significantly higher in cough patients compared to normal subjects and there was a positive correlation between TGF-β levels in BAL and basement membrane thickening.TGFβ in the airways may be important in the airway remodelling changes observed in chronic idiopathic cough patients, that could in turn lead to activation of the cough reflex.

Nonacid Reflux Episodes Reaching the Pharynx are Important Factors Associated With Cough

Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

Assessment and Management of Patients with Chronic Cough by Certified Respiratory Educators: A Randomized Controlled Trial

The value of other health care professionals is increasingly being recognized to compensate for the shortage of physicians in Canada. Chronic cough is one of the most common reasons for consultation with a respirologist. In the present study, a prospective, randomized, controlled study was undertaken to determine whether Certified Respiratory Educators (CREs) could manage screened patients with chronic cough as effectively as respirologists. An eight-week, prospective, parallel-design, randomized, controlled trial of the management of chronic cough patients was conducted. Patients were screened to exclude those with potentially life-threatening conditions. The primary outcome was the number of patients whose cough resolved or subjectively improved. A total of 198 patients were randomly assigned, and eight-week data were available on 151 patients. Mean age of the patients was 49.8+/-13.4 years, 70.2% were female and median cough duration was 16 months. The screening process was effective and referral wait times decreased from a median of two months to less than four weeks (P<0.0001). The educators averaged 4.9 contacts per patient compared with 2.7 by the physicians over the eight-week study period (P<0.0001). Most patients had had multiple therapeutic trials before referral. Cough resolved or improved in two-thirds of the patients at eight weeks; however, more patients showed improvement in the educator arm than in the physician arm, P<0.02. Cough-specific quality of life improved similarly in the two study arms at eight weeks (physician arm: 61.5+/-14.1 to 52.6+/-14.4, P<0.0001; CRE arm: 58.1+/-14.9 to 50.0+/-15.8, P=0.0003). CREs can safely and effectively assess, as well as appropriately treat, screened patients with chronic cough with a resultant reduction in wait times.

Gastroesophageal scintigraphy in the evaluation of adult patients with chronic cough due to gastroesophageal reflux disease

The aim of this study was to evaluate the findings of gastroesophageal scintigraphy (GES) with late lung imaging in adult patients with chronic cough due to gastroesophageal reflux disease and a group of healthy participants. Fifty-five patients with chronic cough with reflux symptoms, and a control group of 12 healthy participants were examined. All patients had reflux esophagitis documented by upper gastrointestinal endoscopy and histology. All participants underwent laryngoscopic examination and GES. The correlation between gastroesophageal reflux and several related variables was evaluated. Overall, 51 patients (92.7%) had positive GES findings for pathologic reflux; 19 (37.2%) of these patients had proximal reflux; and the remaining 32 (62.7%) had distal reflux. The frequency, duration, and percentage volume of gastric content of reflux episodes were significantly greater in patients with proximal reflux than in patients with distal reflux (P<0.0001). No statistically significant differences were seen between proximal reflux and distal reflux patients in terms of pulmonary function parameters, duration of cough, and reflux symptoms scores. However, severe grade (B and C) of esophagitis and the posterior laryngitis were more common in the patients with proximal reflux. Late lung imaging demonstrated evidence of pulmonary aspiration in only three of 51 (6%) patients. Our study suggests that GES with late lung imaging objectively showed the presence of pathologic distal and/or proximal reflux, but rarely pulmonary aspiration, in the majority of chronic cough patients with gastroesophageal reflux disease. As the chronic cough patients with proximal reflux have more severe reflux characteristics, this examination may be effective in screening and following up these patients.

Are there clinical features of a sensitized cough reflex?

Cough reflex hypersensitization is a key feature in patients with troublesome cough. The clinical consequence of this hypersensitive state is typified by bouts of coughing often triggered by low threshold stimuli encountered by the patient during normal daily activities including exposure to aerosols, scents and odours, a change in air temperature and when talking or laughing. These features are often perceived by cough patients to be the most disruptive aspect of their condition and undoubtedly contribute to impaired quality of life. Patients with troublesome cough may describe a range of additional symptoms and sensations including an ‘urge to cough’ or the feeling of an ‘itch’ at the back of the throat, or a choking sensation and occasionally chest pain or breathlessness. It is uncertain if these features arise due to the processes responsible for cough reflex sensitization or as a direct consequence of the underlying cough aetiology. In an attempt to understand the clinical features of a sensitized cough reflex, the spectrum of symptoms typically described by cough patients will be reviewed and possible underlying mechanisms considered. Since an intact cough reflex is crucial to airway protection, anti-tussive treatment that attenuates the hypersensitive cough state rather than abolishing the cough reflex completely would be preferable. Identifying such agents remains a clinical, scientific and pharmacological challenge.

Gender difference in knowledge of tuberculosis and associated health-care seeking behaviors: a cross-sectional study in a rural area of China

BackgroundTuberculosis (TB) detection under the national TB control program in China follows passive case-finding guidelines, which could be influenced by the accessibility of health service and patient's health-care seeking behaviors. One intriguing topic is the correlation between men and women's knowledge on TB and their health-care seeking behaviors.MethodsTwo cross-sectional studies were separately carried out in Yangzhong County, a rural area of China. One study, by using systematic sampling method, including 1,200 subjects, was conducted to investigate the TB knowledge among general population. Another study in the same source population screened 33,549 people aged 15 years or over among 20 stratified cluster-sampled villages for identifying prolonged cough patients at households and individual interviews were then carried out. Gender difference in the knowledge of TB and health-care seeking behaviors was analyzed particularly.ResultsAmong general population, only 16.0% (men 17.1% vs. women 15.0%) knew the prolonged cough with the duration of 3 weeks or longer was a symptom for suspicious TB. Fewer women than men knew the local appointed health facility for TB diagnosis and treatment as well as the current free TB service policy. Moreover, women were less likely to learn information about TB and share it with others on their own initiatives. On the contrary, after the onset of the prolonged cough, women (79.2%) were more likely to seek health-care than men (58.6%) did. However, a large part of women preferred to visit the lower level non-hospital health facilities at first such as village clinics and drugstores.ConclusionTB and DOTS program were not well known by rural Chinese. Gender issues should be considered to reduce diagnostic delay of TB and improve both men and women's access to qualified health facility for TB care. Strengthening awareness of TB and improving the accessibility of health-care service is essential in TB control strategy, especially under the current vertical TB control system.

Hypertonic saline cough provocation test with salbutamol pre‐treatment: evidence for sensorineural dysfunction in asthma

Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. Nineteen healthy subjects, 21 non-asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre-treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough-provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.

Awake palliative thoracic surgery in a high‐risk patient: one‐lung, non‐invasive ventilation combined with epidural blockade

We report the case of a terminally ill cancer patient with recurrent pericardial and bilateral pleural effusions who was scheduled for video-assisted thoracoscopic surgery. The operation was performed with the patient awake under epidural anaesthesia. The patient's cough reflex in response to lung manipulation was successfully minimised by the inhalation of aerosolised lidocaine. Video-assisted thoracic surgery requires the exclusion of a lung from ventilation. In order to support one-lung spontaneous ventilation in this high-risk patient, we successfully used non-invasive bilevel positive airway pressure ventilation via a facemask. Based on this preliminary experience, we think that critically ill patients scheduled for palliative surgery can be successfully managed with the combination of minimally invasive surgical techniques and neuraxial block with non-invasive lung ventilation.

Cough Efficacy Is Related to the Disability Status in Patients with Multiple Sclerosis

Background: Cough is an important defense mechanism, whose main function is to remove mucus and/or foreign bodies from the airways. In patients with multiple sclerosis (MS), respiratory muscle function may be affected and cough may be impaired. Objectives: Respiratory muscle strength and voluntary cough efficacy were determined in MS patients and controls, and the relationship between cough efficacy and patients’ degree of disability was investigated. Methods: We recruited 27 MS patients (age: 41 ± 11 years; 18 females) with mild-to-moderate disability, Expanded Disability Status Scale (EDSS) score range: 1–7, and 20 healthy controls (age: 37 ± 11 years; 12 females). The maximal inspiratory (PIMAX) and expiratory (PEMAX) pressures, maximal whistle mouth pressures (PMOW), cough peak flows (CPF), cough expiratory volumes (CEV) and cough gastric pressures (PGA) were measured in all subjects. Results: In MS patients, the EDSS score was significantly related to CPF, PEMAX, PMOW, cough PGA, PIMAX and CEV (p < 0.01, each correlation). The receiver-operating characteristic curve showed that an EDSS score ≧5.5 was consistent with impaired cough (CPF ≤5.6 l/s), with a sensitivity of 0.85 and a specificity of 0.95 (area under curve 0.90, p < 0.001). CPF was related to and predicted by PEMAX, PMOW, cough PGA and PIMAX in MS patients (p < 0.01 each correlation), but not in controls. Conclusions: MS can affect voluntary cough efficacy and respiratory muscle strength, which are inversely related to the patients’ degree of disability. In addition, this study shows that CPF is a measure of clinical relevance in MS patients.