Airway inflammation and cough sensitivity in cough-variant asthma.

BACKGROUND: Mechanisms underlying cough and bronchoconstriction in patients with cough-variant asthma (CVA) are not well established. Differences in location or degree of activation of eosinophils and allergic cytokines have been suggested as the likely causes. To address this issue, we have carried out a comparative study of airway inflammatory markers between patients with CVA and classic asthma (CA). The relationship between these markers with airway hyperresponsiveness (AHR) and cough sensitivity has also been studied. METHODS: Twenty-seven non-smokers and steroid-naive patients with CVA (12) and CA (15) were examined. Capsaicin challenge, histamine bronchoprovocation test, nitric oxide levels in exhaled air and sputum induction were performed in all of them. Differential cell sputum recount and supernatant concentrations of eosinophil granule-derived cationic proteins (ECP), interleukin (IL)5, IL8 and tumour necrosis factor (TNF)-alpha were also measured. RESULTS: There were no significant differences in either the inflammatory pattern of soluble markers or differential cell counts between CA and CVA. Histamine PC20 was correlated with IL-5 in CVA, whereas it was associated with sputum eosinophilia in CA. Cough sensitivity (log C5) and histamine PC20 were inversely related in CA. CONCLUSIONS: Although the pattern of inflammatory sputum markers in patients with asthma and cough-variant asthma is similar, its relation with bronchial hyperreactivity and cough sensitivity is different in each group.

[Efficacy of an antibacterial filter for preventing contamination of respiratory function diagnostic equipment]. / Eficacia de un filtro antibacteriano en la prevención de la contaminación de equipos de exploración funcional respiratoria.

OBJECTIVES: Devices to assess lung function are a potential source of nosocomial infection. Our aims in this study were: 1) to determine the efficacy of an antimicrobial filter to prevent contamination of a multifunctional device; 2) to assess the ability of the filter to prevent cross contamination of individuals being tested; and 3) to evaluate the efficacy of the recommendations of the Spanish Society of Respiratory Diseases and Thoracic Surgery for disinfecting lung function equipment. DESIGN: In this prospective, randomized study in two phases we used filters in phase 1 but not in phase 2. A pharyngeal swab culture was started within 7 days of a patient's lung function test. Swab samples for culturing were taken from three different places in the equipment at the beginning and end of each working day. PATIENTS: Sixty-five patients (31 in phase 1 and 34 in phase 2) were studied. Thirty-two (49.2%) were men and the mean age was 49.4 15.7 years. RESULTS: Significantly less equipment contamination was found in phase 1 (4.2%) than in phase 2 (21%). We detected no cases of cross contamination using the criteria in this study. No cultures from any of the samples taken before exploration were positive. CONCLUSIONS: a) The antimicrobial filter used is effective for preventing the contamination of lung function testing equipment, b) throughout both phases of the study, we observed no cross contamination of patients tested, such that we cannot conclude that the antimicrobial filter is effective for preventing possible nosocomial infections, c) the recommendations of SEPAR for disinfecting lung function equipment are effective.

Eficacia de un filtro antibacteriano en la prevenciónde la contaminación de equipos de exploraciónfuncional respiratoria / Efficacy of an antibacterial filter for preventing contamination of respiratory function diagnostic equipment

OBJETIVOS: Los equipos de evaluación de la función respiratoria constituyen una potencial fuente de infección nosocomial. En este estudio nos hemos propuesto: a) comprobar la eficacia de un filtro antimicrobiano en la prevención de la contaminación de un equipo multifunción; b) valorar la capacidad del filtro utilizado para evitar la contaminación cruzada entre los individuos que se exploran, y c) evaluar la efectividad de las recomendaciones de desinfección SEPAR para equipos de función pulmonar. DISEÑO: Realizamos un estudio prospectivo, aleatorio, que constó de dos fases: en la fase I utilizando filtros y en la fase II sin filtros. Llevamos a cabo frotis faríngeo, antes y a los 7 días de realizar un estudio de función pulmonar. También tomamos muestras (frotis) de tres puntos diferentes del equipo para su cultivo, al inicio y al final de cada jornada de trabajo. PACIENTES: Se incluyó en el estudio a 65 pacientes (31 en la fase I y 34 en la fase II), 32 de ellos varones (49,2 por ciento). La edad fue de 49,4 ñ 15,7 años. RESULTADOS: Encontramos contaminación del equipo en el 4,2 por ciento de las muestras en la fase I, cifra significativamente menor que la del 21 por ciento de la fase II. No detectamos, con el criterio empleado, ningún caso de contaminación cruzada. No obtuvimos cultivos positivos en ninguna muestra realizada antes de comenzar las sesiones de exploración. CONCLUSIONES: El filtro antimicrobiano utilizado es eficaz en la prevención de la contaminación del equipo de exploración funcional. No observamos contaminación cruzada en ninguno de los pacientes que exploramos durante todo el estudio, por lo que no podemos afirmar que el filtro antimicrobiano sea eficaz como medio de prevención de la potencial infección nosocomial. Las recomendaciones SEPAR son eficientes para desinfectar los equipos de función pulmonar (AU)

Cough reflex testing with inhaled capsaicin in the study of chronic cough.

OBJECTIVES: To assess the utility of capsaicin test in the differential diagnosis of non-productive causes of chronic cough and to examine the effects of treatment on this reflex. PARTICIPANTS: 86 healthy volunteers and 101 patients with chronic cough: asthma (n: 54) gastroesophageal reflux (n: 35) and post-nasal drip syndrome (n: 12). DESIGN: Prospective intervention trial. Spirometry, bronchoprovocation test with histamine (PC20), and cough challenge with ascending concentrations of capsaicin (0.49-500 microM) were initially performed in all subjects. Patients were treated for 3 months according to the origin of the cough. Concentrations that elicited two (C2) and five or more coughs (C5) were determined before and after treatment. RESULTS: In healthy subjects, cough sensitivity to capsaicin was not influenced by gender or smoking status; however, women with chronic cough were more sensitive to cough challenge than men. C2 and C5 were significantly lower in patients with asthma or gastroesophageal reflux than in post-nasal drip syndrome. No significant correlation was observed between the capsaicin cough threshold and PC20. Cough sensitivity did not improve significantly in most patients with asthma or gastroesophageal reflux despite adequate medical treatment during 3 months. Discriminative value of capsaicin test to differentiate healthy subjects from patients with asthma or reflux was poor. CONCLUSIONS: Cough sensitivity to inhaled capsaicin is a safe and reproducible tool in the study of chronic cough. However, its usefulness for the management and differential diagnosis is limited.

Noninvasive positive pressure home ventilation in restrictive disorders: outcome and impact on health-related quality of life.

Noninvasive positive-pressure home ventilation (NIPPHV) improves arterial blood gases, dyspnea and health-related quality of life (HRQL) in patients with restrictive thoracic diseases. Whether these changes persist during the follow-up remains unclear. The aim of this study was to investigate the long-term effects of NIPPHV upon dyspnea, HRQL, lung function and hospitalization rate in 35 patients with kyphoscoliosis and 27 individuals with several neuromuscular disorders. So, we measured dyspnea, HRQL, lung function and nocturnal oxygen saturation (SaO2) before and after 3, 6, 9, 12 and 18 months after NIPPHV. Dyspnea was assessed with the Borg scale and HRQL was measured using the Spanish validated version of the SF-36 questionnaire. The kyphoscoliosis group showed significant improvement of PaCO2 and SaO2 at 3 months and minor dyspnea changes at 6 months after NIPPHV had been started. These patients also showed improved health status in the following categories: "physical role" and "emotional role" at 3 months and in the categories "social functioning", "vitality" and "mental health" at 6 months after NIPPHV; some of these changes persisted at 9, 12 and 18 months. In the neuromuscular group, a significant improvement of SaO2 was observed at 3 months and this persisted for 18 months. Changes of HRQL in this group included a significant improvement in "physical role" at 3 months, "emotional role" and "social functioning" at 6 months and "physical functioning" at 9 months. The hospitalization rate decreased significantly in all patients from a mean annual admission rate of 1.1 (1.4) before NIPPHV to 0.6 (1.1) after 12 months of ventilatory support (P<0.005). We conclude that: (a) NIPPHV had a higher impact on arterial blood gases, dyspnea and health-related quality of life in patients with kyphoscoliosis than in those with neuromuscular disorders; (b) most clinical and functional changes persisted at long term and (c) a significant decrease in the hospitalization rate after NIPPHV occurred in both groups.

Prevalence of gastroesophageal reflux in asthma.

A high prevalence of gastroesophageal reflux disease (GER) in asthma patients has been shown in several reports from North America and Europe. However, no data from Southern Europe are available. This paper evaluates the prevalence of abnormal reflux in asthmatics, the pattern of acid reflux when present, and the relationship between asthma and GER. Eighty-one consecutive ambulatory patients with clinically stable asthma (41 women; median age 40 years, range 17-69 years) were prospectively evaluated. All patients had a thorough digestive history; baseline pulmonary function studies, including bronchoprovocation methacholine test; and ambulatory 24-hr esophageal pH monitoring. Reflux symptoms were present in 40 patients (49%). Twelve patients had abnormal GER as defined by pH testing, giving a prevalence rate of 15% (95% confidence interval 8%-24%). The presence of acid reflux was not associated with a more severe respiratory disease. Abnormal GER seems not to be a clinically significant problem in many patients with asthma in our area.

Assessment of the reliability, validity, and responsiveness of a Spanish Asthma Quality of Life questionnaire.

A Spanish-language questionnaire designed for measuring the impact of asthma on quality of life in adults was developed. It was derived, by the application of a rigorous translation protocol, from a previously validated, English-language Asthma Quality of Life (AQL) questionnaire which had been developed in Australia. The aim of this study was to evaluate the psychometric properties of the Spanish AQL questionnaire using a cross-sectional and longitudinal design. Two hundred ninety-four clinically stable subjects with asthma (168 women, mean baseline forced expiratory volume in 1 sec [FEV1] = 85% predicted), aged 17-70, attended for the initial baseline assessment. All subjects completed the AQL questionnaire and a full history and physical examination were performed. The clinical assessment of severity was based on the classification recommended by the Global Initiative on Asthma (GINA). One week after the initial assessment subjects completed the AQL questionnaire for a second time. Six months later, subjects were assessed clinically and completed all the assessment measures at baseline. Principal components analysis of the AQL questionnaire responses at the baseline visit revealed a structure that was almost identical to that seen in the original English-language questionnaire. The questionnaire was shown to be internally consistent (Cronbach's alpha 0.91 for total score and 0.80-0.86 for the four subscales) and repeatable (intraclass correlation coefficient 0.91 for the total scale and 0.78-0.92 for the subscales). The finding of expected strong correlations with the subject's global assessment of severity (p = 0.70) and dyspnea (p = 0.63), a weak inverse correlation with FEV1 (p = -0.17), and good discrimination among the four GINA severity categories (F3,291 = 37.16, p < 0.0001) supports the construct validity of the questionnaire. AQL scores increased with age (p = 0.31) and were higher in women (p < 0.005). The AQL was responsive to both improvement (mean change 1.02, p < 0.0001) and deterioration (mean change -1.13, p < 0.001) in the severity of asthma over a 6-month period. This disease-specific, Spanish-language AQL questionnaire was shown to have sound psychometric properties which make it suitable for use in cross-sectional or longitudinal studies where it is appropriate to assess the impact of asthma on the quality of life of individual patients.

[Treatment of asthmatic crises at a hospital emergency service. Are the protocols followed?]. / Tratamiento de la crisis asmática en un servicio de urgencias hospitalario. Se cumplen las normativas?

Improper assessment and treatment of asthma attacks have been identified as causes of increased morbidity and mortality: several pneumological societies have therefore created and published guidelines for facilitating decision making and for preventing unnecessary failures of therapy. The objective of this study was to examine emergency department compliance with such guidelines in our hospital, comparing the performance of pneumologists and other specialists. We reviewed the records of 117 patients treated for acute asthma attacks in 1994 (87 women and 30 men, mean age 46 years); 37 patients were treated by pneumologists and 80 by other specialists. The two physician groups differed significantly with respect to initial assessment of severity, particularly in the recording of vital signs (p < 0.05) and in the examination of some signs such as the use of accessory musculature (38% versus 10%, for pneumologists and other specialists, respectively) or the presence of cyanosis (81% versus 55%). Other factors associated with risk of death were noted only occasionally. Peak flow meters were used with only 5 patients, all examined by pneumologists; on the other hand, arterial blood samples for gasometric measurements were taken from 97%, although only 24% met the criteria stipulated in the guidelines. Treatment evaluated against the guidelines was incorrect in 24%, with no significant differences between pneumologists and other specialists. We conclude that: 1) the emergency clinical assessment and treatment of patients presenting with acute asthma attack is inadequate for a large proportion of patients, as the recommendations of consensual guidelines are habitually ignored, and 2) although there are differences in the management of these patients by pneumologists and other emergency room specialists, the former do not generally do a better job of following the guidelines.

Prediction of the need for mechanical ventilation in acute severe asthma.

Unwarranted long delays in treating asthmatic patients requiring assisted mechanical ventilation (AMV) could be associated with higher death rates. The objective of the study was to identify which were the best predictive characteristics of patients with acute severe asthma (ASA) who required AMV. For this purpose, we reviewed retrospectively the hospital record of every patient with ASA admitted to the intensive care unit (ICU) from 1981 to 1991 (38 with AMV and 38 without AMV). Twenty-seven variables were obtained from the history, physical examination, laboratory tests, blood gases and treatment. Using a multivariate discriminant analysis, the most powerful predictor of patients needing AMV was a function that consisted of eight variables: arterial pH, number of previous admissions to ICU, asthma severity, time elapsed since last visiting a physician, respiratory rate, age, systolic pressure and heart rate. With this function, 33 of 38 mechanically ventilated patients were well classified (sensitivity: 0.89) and the overall accuracy of the test was 92% (70 out of 76 cases). The positive and negative predictive values of the function for mechanical ventilation were 0.96 and 0.90, respectively. We conclude that the application of the calculated final discriminant function could be appropriate to decide which patients with ASA require AMV.

Effect of serotonin and calcium in normal and sensitized guinea pig isolated trachea.

Tracheal strips from normal and actively sensitized guinea pigs were studied to determine the responses to serotonin (5-hydroxytryptamine, 5-HT; 1 nM-0.1 mM) and ouabain (0.1 microM-0.1 mM), and the effects of increasing the extracellular calcium (Cao) concentration on tonic contractions elicited by 5-HT. Sensitized trachea exhibited an increased responsiveness and sensitivity to 5-HT and ouabain. Increases in Cao to achieve final concentrations of 5, 10 and 20 mM caused concentration-related relaxations of normal and sensitized tissues contracted to a similar plateau level with 5-HT. Inhibition of the Na+/K(+)-ATPase by ouabain (10 microM) reversed the effects of Cao from relaxation to contraction in normal and sensitized tissues contracted with 5HT. Sensitized preparations showed reduced relaxations in response to Cao (10-20 mM), and sensitized, ouabain-treated, trachea showed augmented contractions to Cao (10-20 mM) when compared to normal tissues. These results demonstrate a decreased membrane-stabilizing effect of Cao in sensitized trachea and the implication of the Na+/K(+)-ATPase in the regulation of membrane stability by Cao, suggesting a possible relevance to those mechanisms underlying airway hyperreactivity.

[The quality of life in asthma: an evaluation of the AQLQ questionnaire for its use on a Spanish population. Asthma Quality of Life Questionnaire]. / Calidad de vida en el asma: validación del cuestionario AQLQ para su utilización en población española.

The study of morbidity in asthma requires consideration not only of standard physiopathologic and function parameters, but also of the impact the disease has on the patient's life-style as he or she perceives it and evaluates it. The quantification of this factor, known as health-related quality of life (HRQL), is achieved by administering questionnaires specially designed for the purpose. We analyzed the reliability, content validity and construct validity (convergence and divergence) of one instrument, the Asthma Quality of Life Questionnaire (AQLQ) designed by Marks and colleagues. This questionnaire covers 4 dimensions (breathlessness, mood, social limitation and worrying) and gives a total score. After a process of translation and back translation the AQLQ was administered to 102 adult asthmatics living in an urban center, all of whom had been stable for at least the preceding 4 weeks. The following data were recorded: age, sex, duration of disease, FEV1, medication, dyspnea, hospital visits, nighttime symptoms and severity of disease (from the patient's own point of view and according to the scale of the International Consensus Report [ICR]). The reliability study (internal consistency with Crombach's alpha coefficient and inter-item correlation analysis) gave satisfactory results in all cases (range of r = 0.39 to 0.78; alpha = 0.78 to 0.91). Content validity (factorial analysis of the main components, oblique and orthogonal rotations) was less satisfactory, although 4 factors were found; these factors adjusted relatively well to one of the proposed sub-scales and together explained 65.2% of the total variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial asthma and personality dimensions: a multifaceted association.

Personality dimensions seem to play an important role in chronic diseases by maintaining or increasing the patient's physical complaints. This study examines in bronchial asthma: (a) the relationships among clinical data, baseline lung function, and personality traits; and (b) the patient's characteristics related to the physician's judgement about his or her asthma severity. Five questionnaires measuring anxiety, depression, self-consciousness, and subjective symptoms were completed by 51 asthmatic patients. Responses to questionnaires and clinical and demographic data were factor-analyzed. Factor analysis revealed that the physician's severity judgement is based on elderly age, high scores on depression, and longer duration of asthma.

Diagnostic value of the bronchial provocation test with methacholine in asthma. A Bayesian analysis approach.

The Bayesian analysis was used in this study to investigate the diagnostic value of the bronchial provocation test with methacholine in patients with asthma. The best cutoff value of accumulated concentration of methacholine administered that caused a 20 percent fall in FEV1 post-saline (PC20) in our sample, determined with a receiver operator characteristic curve, was 15 mg/ml. The interval security of the test was established by a pretest probability between 0.16 and 0.87 and the best test results were obtained when pretest probability was 0.48. The positive final diagnostic gain of the test was maximal at this pretest probability. We conclude that the application of Bayes' theorem, considering the pretest probability of asthma and the sensitivity and specificity of the individual PC20 obtained, increases the accuracy of the bronchial provocation test with methacholine in the diagnosis of asthma.

Usefulness of carcinoembryonic antigen determination in bronchoalveolar lavage fluid. A comparative study among patients with peripheral lung cancer, pneumonia, and healthy individuals.

We compared carcinoembryonic antigen (CEA) levels in bronchoalveolar lavage (BAL) fluid and serum of patients with lung cancer, pneumonia, and healthy individuals to determine the usefulness of CEA in diagnosing lung cancer not visible endoscopically. Cancer patients had CEA lavage fluid levels (4,650 +/- 1,565 ng/mg of albumin) significantly higher than pneumonia patients (755 +/- 346 ng/mg) or healthy individuals, smokers (252 +/- 48 ng/ml), and non-smokers (175 +/- 6 ng/mg). In serum, CEA assay cannot discern between cancer (35 +/- 13 ng/ml) and pneumonia (4.6 +/- 1.4 ng/ml) (p = 0.06). Using 1,000 ng/mg of albumin as the cutting point in BAL fluid, sensitivity and specificity were 77 percent and 94 percent, respectively. In serum, 5 ng/ml provided a sensitivity of 55 percent and specificity of 91 percent. Positive and negative predictive values were 77 percent and 94 percent in BAL, respectively, and 62 percent and 89 percent in serum, respectively. Using a combination of serum and BAL fluid CEA levels, the sensitivity and specificity were 88 percent and positive and negative predictive values were 66 percent and 96 percent, respectively. When used in combination with serum levels of CEA or transbronchial biopsy, the diagnostic yield increased up to 88 percent. Thus, although CEA determination in BAL fluid improves diagnostic yield, it should not be used as the only diagnostic procedure.