Julio Marín

The 6-min walk distance in healthy subjects: reference standards from seven countries

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40–80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HRmax) during the 6-min walk test/the predicted maximum HR (HRmax % pred), Borg dyspnoea score and oxygen saturation. The mean±sd 6MWD was 571±90 m (range 380–782 m). Males walked 30 m more than females (p<0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HRmax % pred (adjusted r2 = 0.38; p<0.001), but there was variability across centres (adjusted r2 = 0.09–0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p<0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects

Obstructive sleep apnoea (OSA) occurs because of recurrent narrowing and occlusion of the velopharynx (VP) during sleep. The specific cause of OSA is unknown. Cephalometric radiography, fibreoptic nasopharyngoscopy, acoustic reflection techniques, and computerized tomography have limitations (dynamic and tridimensional evaluation) in the mechanism of occlusion investigation. Static and dynamic examination of the soft tissue structures surrounding the upper airway during the respiratory cycle in wakefulness and sleep, can lead to a better understanding of the process. Ultrafast magnetic resonance imaging (one image per 0.8 s) was used to study the upper airway and surrounding soft tissue in 17 patients with OSA during wakefulness and sleep, and in eight healthy subjects whilst awake. The major findings of this investigation in the 25 subjects were as follows: 1) the VP was smaller in apnoeic patients, only during part of the respiratory cycle; 2) the variation in VP area during the respiratory cycle was greater in apnoeic patients than in controls, particularly during sleep, suggesting an increased compliance of the VP in these patients; 3) VP narrowing was similar in the lateral and anterior-posterior dimensions, both in controls and apnoeic patients while awake; apnoeic patients during sleep have a more circular VP upon reaching the minimum area; 4) there was an inverse relationship between dimensions of the lateral pharyngeal walls and airway area, probably indicating that lateral walls are passively compressed or stretched as a result of changes in the airway calibre; and 5) soft palate and parapharyngeal fatpads were larger in apnoeic patients, although their role in the genesis of OSA is uncertain. It was concluded that changes in the velopharynx area and diameter during the respiratory cycle are greater in apnoeic patients than in normal subjects, particularly during sleep. This suggests that apnoeic patients have a more collapsible velopharynx, this being the main mechanism of obstruction.

The 6-min walking distance: long-term follow up in patients with COPD

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160–600 m). It declined by 19% (16 m·yr-1) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30–50% predicted) and by 26% (15 m·yr-1) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.

Validation and comparison of reference equations for the 6-min walk distance test

Exercise impairment as measured by the 6-min walk distance (6MWD) test afflicts many patients with chronic obstructive pulmonary disease (COPD) and is known to predict mortality. Reference equations for the 6MWD in adults have been published but not yet validated. The present authors prospectively followed 1,379 COPD patients for 55±30 months and tested the predictive value of the baseline 6MWD in metres, the 6MWD work (kg·m−1) and as a percentage of predicted values the 6MWD in meters according to two reference equations. All-cause mortality was the validating outcome. The best threshold values were identified for each of the tests using receiver operating characteristic (ROC) curves. The threshold values obtained were: 350 m for the 6MWD, 25,000 kg·m−1 for the 6MWD work, and 67 and 54% predicted for the two reference equations. All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test. In conclusion, all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well. In the 6-min walk distance test, a value <350 m is associated with increased mortality and should be regarded as abnormal.

Sex differences in mortality in patients with COPD

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George’s Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan–Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.

The modified BODE index: validation with mortality in COPD

Peak oxygen uptake (V′O2) remains the gold standard measurement of exercise capacity and has been associated with survival. A modified BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index replacing the 6-min walk distance (6MWD) with V′O2 as % predicted (mBODE%) has been developed and found to have excellent correlation with the conventional BODE index. The objectives of the present study were to compare the ability of the conventional BODE and the mBODE% to predict mortality in 444 patients with chronic obstructive pulmonary disease (COPD) followed for a mean±sd period of 71±34 months. Anthropometrics, spirometry, lung volumes, comorbidity, cardiopulmonary cyclo-ergometry test and 6MWD were determined at entry. The mean BODE indices for the cohort were: BODE 4.1±2 and mBODE% 5.5±2. Both indices were significantly correlated with mortality. Logistic regression analysis with COPD survival as the dependent variable identified the BODE index, Charlsons and exercise capacity (in W) as variables associated with this outcome. In conclusion, the conventional BODE index, which uses the 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease as well as the modified index using peak oxygen uptake. The results support the use of the simpler index, which includes the 6-min walk distance in the comprehensive evaluation of patients with chronic obstructive pulmonary disease.

Mechanical insufflation-exsufflation vs. tracheal suctioning via tracheostomy tubes for patients with amyotrophic lateral sclerosis: a pilot study.

Sancho J, Servera E, Vergara P, Marín J: Mechanical insufflation-exsufflation vs. tracheal suctioning via tracheostomy tubes for patients with amyotrophic lateral sclerosis: A pilot study. Am J Phys Med Rehabil 2003;82:750–753. Objective To compare the effects of mechanical insufflation-exsufflation vs. suctioning via tracheostomy tubes on respiratory variables for six amyotrophic lateral sclerosis patients. Design In this prospective crossover study, six consecutive patients with amyotrophic lateral sclerosis who required continuous mechanical ventilation via tracheostomy tubes and developed chest infections underwent measurement of pulse oxyhemoglobin saturation (SpO2), peak inspiratory pressure (PIP), mean airway pressure (Pawm), and work of breathing performed by the ventilator (WOBv) at baseline and 5 and 30 min after tracheal suctioning and 5 min after mechanical insufflation-exsufflation. Results The baseline values were 93.50 ± 2.26% for SpO2 in ambient air, 18.50 ± 4.23 cm H2O for PIP, 4.67 ± 1.37 cm H2O for Pawm, and 1.03 ± 0.25 J/liters for WOBv. Only WOBv changed significantly, decreasing after tracheal suctioning (P < 0.05), whereas all variables improved significantly after mechanical insufflation-exsufflation. Conclusion For ventilator-dependent patients with amyotrophic lateral sclerosis, mechanical insufflation-exsufflation via a tracheostomy tube with an inflated cuff may be more effective in eliminating airway secretions than conventional tracheal suctioning.

Alternatives to endotracheal intubation for patients with neuromuscular diseases.

Servera E, Sancho J, Zafra MJ, Catalá A, Vergara P, Marín J: Alternatives to endotracheal intubation for patients with neuromuscular diseases. Am J Phys Med Rehabil 2005;84:851–857. Objective:To evaluate the usefulness of continuous noninvasive mechanical ventilation and mechanical coughing aids to avoid endotracheal intubation and tracheostomy during episodes of acute respiratory failure in patients with neuromuscular disease. Design:We conducted a prospective cohort study at the respiratory medicine ward of a university hospital to study the success rate of the use of continuous noninvasive mechanical ventilation and manually and mechanically (CoughAssist) assisted coughing to avert endotracheal intubation in 24 consecutive episodes of acute respiratory failure for 17 patients with neuromuscular disease. The noninvasive mechanical ventilation and coughing aids were used to reverse decreases in oxyhemoglobin saturation and relieve respiratory distress that occurred despite oxygen therapy and appropriate medication. Noninvasive mechanical ventilation was delivered by volume ventilators (Breas PV 501) alternating nasal/oronasal and oral interfaces. Results:Noninvasive management was successful in averting death and endotracheal intubation in 79.2% of the acute episodes. There were no significant differences in respiratory function between the successfully treated and unsuccessfully treated groups before the current episode. Bulbar dysfunction was the independent risk factor for failure of noninvasive treatment (P < 0.05; odds ratio, 35.99%; 95% confidence interval, 1.71–757.68). Conclusions:Intubation can be avoided for some patients with neuromuscular disease in acute respiratory failure by some combination of noninvasive mechanical ventilation and mechanically assisted coughing. Severe bulbar involvement can limit the effectiveness of noninvasive management. ABBREVIATIONS: ALS: amyotrophic lateral sclerosis; ETI: endotracheal intubation; FEV1: forced expiratory volume in 1 sec; FVC: forced vital capacity; %FVC: percentage predicted FVC; MIC: maximum insufflation capacity; NIV: noninvasive ventilation; NMD: neuromuscular disease; PCF: peak cough flow; PCFMIC: manually assisted PCF; PImax: maximum mouth inspiratory pressure; PEmax: maximum expiratory pressure; SpO2: pulse oxyhemoglobin saturation

Mechanical insufflation-exsufflation: Pressure, volume, and flow relationships and the adequacy of the manufacturer's guidelines

Gómez-Merino E, Sancho J, Marín J, Servera E, Blasco ML, Belda JF, Castro C, Bach JR: Mechanical insufflation-exsufflation: Pressure, volume, and flow relationships and the adequacy of the manufacturer’s guidelines. Am J Phys Med Rehabil 2002:81;579–583. Objective Pulmonary complications of neuromuscular disease can be averted by increasing peak cough flows with the use of a forced exsufflation device. The purpose of this study was to examine the pressure, volume, and flow relationships for a range of settings generated by this device, and compare them with clinically efficacious values and the manufacturer’s guidelines. Methods The In-exsufflator was connected to a standard lung model. The resulting forced deflation volumes, flows, and pressures were averaged over 10 cycles at each setting. Results The set insufflation pressures significantly correlated with the generated insufflation pressures and volumes and the exsufflation volumes and flows. Increasing set insufflation time significantly increased generated insufflation pressures, flows, and volumes and exsufflation volumes. Increasing set exsufflation time did not significantly increase generated exsufflation flows. At set pressures of 40 to −40 cm H2O, insufflation time of 3 sec, and exsufflation time of 2 sec, the exsufflation flow was 4.09 l/sec. A plateau insufflation volume of 3.8 l was reached after 4.9 sec of insufflation. Conclusions In-exsufflator performance was very consistent. Its clinical effectiveness can be explained by its generation of exsufflation flows >2.7 l/sec. Increasing insufflation times more than exsufflation times is more important for optimal function. Current manufacturer use guidelines may not yield optimal exsufflation flows.

Assessment of Analysis of Urinary Pneumococcal Antigen by Immunochromatography for Etiologic Diagnosis of Community-Acquired Pneumonia in Adults

ABSTRACT The limitations of conventional microbiologic methods (CMM) for etiologic diagnosis of community pneumococcal pneumonia have made faster diagnostic techniques necessary. Our aim was to evaluate the usefulness of the immunochromatography (ICT) technique for detecting urinary Streptococcus pneumoniae antigen in the etiologic diagnosis of community-acquired pneumonias (CAP). This was a prospective study on in-patients with CAP in a tertiary hospital conducted from October 2000 to March 2004. Apart from using CMM to reach an etiologic diagnosis, we determined pneumococcal antigen in concentrated urine by ICT. We also determined the urinary pneumococcal antigen (UPA) content in patients from two control groups to calculate the specificity of the technique. One group was comprised of in-patients diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, with respiratory infection, and without pneumonia; the other group included fractures. We studied 959 pneumonia patients and determined UPA content in 911 (95%) of them. We diagnosed the etiology of 253 cases (28%) using CMM; S. pneumoniae was the most common etiologic agent (57 cases). ICT analysis was positive for 279 patients (31%). Using this technique, the percentage of diagnoses of pneumococcal pneumonias increased by 26%, while the overall etiologic diagnosis increased from 28 to 49%. The technique sensitivity was 81%; the specificity oscillated between 80% in CAP with nonpneumococcal etiology and 99% for patients with fractures without infections. Determination of UPA is a rapid, simple analysis with good sensitivity and specificity, which increased the percentage of etiologic diagnoses. Positive UPA may persist in COPD patients with probable pneumococcal colonization or recent pneumococcal infections.