Miguel Perpiñá

Determinants of Dyspnea in Patients with Different Grades of Stable Asthma

Dyspnea is a main feature of symptomatology in asthma, and its perception does not necessarily correlates well with airway obstruction. The aim of this study was twofold: 1 to identify factors determining the subjective degree of dyspnea in patients with different grades of stable bronchial asthma and 2 to compare various clinical methods existing for grading dyspnea. The investigation comprised 153 outpatients with stable asthma. The parameters studied were the following: demographic characteristic of subjects, baseline dyspnea score by means of three clinical instruments (baseline dyspnea index [BDI], Medical Research Council [MRC] scale, and modified Borg scale), asthma severity, standard measures of physiologic lung function, anxiety, depression, subconscious illness attention, and asthma-related quality of life (HRQOL). The dyspnea scores were all significantly interrelated (r = 0.77–0.85, p<0.001). The three clinical scales for grading dyspnea were significantly correlated with the same parameters: airflow obstruction, lung hyperinflation, emotional factors, HRQOL, age, age at asthma onset, asthma duration, female gender, clinical severity, and lower economical, and educational levels. Multiple regression analysis showed that independent factors determining clinical dyspnea scores were: age, airway obstruction, and emotional status. Moreover, in patients with severe asthma, lung hyperinflation helped to explain the individual dyspnea score. These data suggest that clinical methods are appropriate for evaluating the impact of dyspnea on daily activities of asthmatic patients. BDI, MRC, and Borg clinical dyspnea scales showed similarly information in subjects with asthma. Independently of asthma severity, older age, airway obstruction, and psychological disturbance were associated with higher degree of dyspnea. However, if subjects had severe airway obstruction, lung hyperinflation was a major determinant of baseline dyspnea score.

Gender Differences in Health‐Related Quality of Life Among Patients with Asthma

This study has a twofold objective: 1) to explore to what extent suffering from asthma affects the HRQL of men and women differently at several stages of disease severity and 2) to analyze whether the informed poorer HRQL of asthmatic women is related to their higher scores on instruments measuring emotionally disordered symptoms. One hundred fifty‐one outpatient asthmatics (84 women and 67 men) completed the Spanish versions of the Asthma Quality of Life questionnaire (AQL), as well as anxiety and depression inventories. A full history, physical examination, and pulmonary function test were performed on all subjects. Patients were classified into one of four asthma severity categories following the criteria of the Global Initiative on Asthma (GINA). There were no gender differences in sociodemographic variables, asthma duration, GINA, FEV1 or dyspnea. However, women showed a poorer HRQL than men, as well as high degrees of anxiety and depression. When these data were reanalyzed taking into account the four groups of asthma severity, women only reported a poorer HRQL than men at the intermittent asthma level. The gender differences on depression and anxiety scores were maintained at the three lower severity levels, but not at the most severe asthma degree. When depression and anxiety scores were partialed out, the AQL scores maintained significant relationships with asthma severity, dyspnea, and FEV1, both in women and men. Therefore, only in men were there also relationships among AQL and sociodemographic data. The best predictor of the womens HRQL was the dyspnea score, whereas in men it was the asthma severity (GINA).

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.

Non-specific hyperreactivity to pharmacological stimuli in tracheal and lung parenchymal strips of actively sensitized guinea-pigs

The responsiveness of tracheal and lung parenchymal strips isolated from actively sensitized guinea‐pigs to CaCl2 (in K+‐depolarized tissue), KCl, acetylcholine and histamine was compared with that of strips from unsensitized animals. The concentration‐response curves to the mentioned agonists exhibited, in the sensitized group, a left upward displacement (greater maximal effect, lesser effective concentration 50% and a steeper slope) compared with those obtained in the unsensitized group. These results indicate the existence of a non‐specific increase in responsiveness in the airway smooth muscle from sensitized animals.

Effects of Erythromycin on Chemoattractant- Activated Human Polymorphonuclear Leukocytes

1. Erythromycin (2-100 micrograms ml-1) produced a concentration-related inhibition of superoxide generation and elastase release induced by in vitro exposure of human polymorphonuclear leukocytes (PMNs) to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP; 30 nM). 2. By contrast, erythromycin (100 micrograms ml-1) did not alter the leukotriene B4 production elicited by FMLP (30 nM; in the presence of thimerosal 20 microM) or the intracellular calcium changes promoted by FMLP (30 nM; in the absence or presence of thimerosal 20 microM). 3. These results indicate that by reducing chemoattractant-triggered release of oxidative and proteolytic mediators from human PMNs, erythromycin may have clinically useful antiinflammatory effects.

Prevalence of Malnutrition in Outpatients With Stable Chronic Obstructive Pulmonary Disease

OBJECTIVE To determine the prevalence of malnutrition in outpatients with stable chronic obstructive pulmonary disease (COPD) followed at a respiratory clinic. MATERIAL AND METHOD In this prospective study, we assessed the nutritional status of consecutive outpatients with stable COPD by investigating various anthropometric parameters. Patients were malnourished (low body weight) if their body mass index was within the bottom quartile of a reference population. Muscle mass was determined from the midarm muscle area and if this mass was at or within the bottom quartile, muscle wasting was present. Albumin and transferrin plasma concentrations were used as a measure of visceral protein stores. Fat stores were assessed from body fat and if this value was at or within the bottom quartile, calorific malnutrition was present. All patients underwent arterial blood gas sampling at rest and spirometry. RESULTS A total of 178 patients--one woman (0.6%) and 177 men (99.4%)--were enrolled in the study, with a mean (SD) age of 69 (9) years. We found low body weight in 19.1% of the patients, muscle wasting in 47.2%, visceral protein depletion in 17.4%, and fat depletion in 19.1%. Of the patients with normal weight, 62.9% showed muscle wasting. The proportion of patients with a body mass index or midarm muscle area at or within the bottom quartile increased significantly with increased bronchial obstruction (P<.001 and P=.015, respectively), though 35.7% of the patients showed muscle wasting even when COPD was mild. CONCLUSIONS Many patients with stable COPD suffer malnutrition. Nutritional state is worse with more severe COPD. Depletion involves both fat stores and muscle and visceral protein stores, but the greatest effect is seen in muscle wasting. A significant number of patients with normal weight also suffer muscle wasting. Although changes in body composition were common in our patients, low body weight was less prevalent than has been reported for populations in countries that are socially and economically similar to Spain.

The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle

SummaryCromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1–30 μmol/l) inhibited the spontaneous tone of human isolated bronchi n a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean ±SEM) was isoprenaline (7.29 ± 0.27; n = 8) > cromakalim (5.89 ± 0.12; n = 7) > theophylline (4.07 ±0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 μmol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppressed the contraction produced by KCI (25 mmol/l) but not that produced by KCl (120 mmol/l). Tetraethylammonium (8 mmol/l) was without effect against the relaxant action of cromakalimbut procaine (0.5 – 5 mmol/l) and glibenclamide (0.3 μmol/l) antagonised it. Cromakalim (10 μmol/l) produced an upward displacement of concentration-effect curves forKCI (1–100 mmol/l), acetylcholine (1 nmol/l-1 mmol/) and histamine (1 nmol/l-1 mmol/l) but it did not alter the concentration-effect curve for LTD4 (0.1 nmol/l-0.1 μmol/l). When tissues were challenged in the presence of cromakalim (10 μmol/l) with KCI (100 mmol/l), acetylcholine (1 mmol/l) or histamine (1 mmol/l), an enhanced contraction was observed compared to control tissues. This enhancement by cromakalim was absent when tissues were challenged with acetylcholine or histamine in either a Ca2+-free medium (plus EGTA 0.1 mmol/l) or in the presence of verapamil (10 μmol/l). It is concluded that cromakalim is an effective relaxant of human airway smooth muscle in vitro and this activity may depend on the opening of K+ channels in the plasma membrane of smooth muscle cells but other actions cannot be ruled out.

Modification by indomethacin of airway contractile responses in normal and sensitized guinea-pigs

Active sensitization of guinea-pigs resulted in an increase in responsiveness and sensitivity of tracheal and lung parenchymal strips to CaCl2 (in K+-depolarised tissue), KCl, acetylcholine and histamine. Indomethacin (5 microM) preferentially enhanced the response of tracheal strips from normal animals to histamine and to a lesser extent acetylcholine but not to CaCl2 or KCl. A similar trend was observed in sensitized tissues. Indomethacin pretreatment did not cause changes in responsiveness or sensitivity of lung parenchymal strips from normal or sensitized guinea-pigs to the agonists tested. It is concluded that immunological sensitization produced a non-specific hyperresponsiveness in trachea and lung parenchymal strips. Conversely, cyclooxygenase inhibition by indomethacin elicited a selective increase in the responsiveness to certain agonists in central but not in the peripheral airways.

Respuesta inflamatoria de la exacerbación asmática de instauración rápida

UNLABELLED The association between onset of asthma exacerbation and the inflammatory response has not been sufficiently studied. OBJECTIVE To determine the differential mechanisms of the rapid onset (RO) asthma exacerbation. METHODS We designed a prospective, multicentre study that included 34 patients who suffered from asthma exacerbation. They were distributed into three groups of asthmatics, depending of the time of onset: from 0 to 24h, from 25 to 144h and more than 145h. We collected clinical data, sputum, blood and urine samples when first seen at the clinic and the next 24h later, and differential cell counts and biomarkers were determined RESULTS The asthmatics who suffered a RO exacerbation showed a higher elastase concentration, (1.028±1.140; 310±364; 401±390ng/ml) (P<0.05) and albumin (46.2±4.3; 42±3.4; 39.9±4.8g/l) (P<0.05) in the blood sample. Neutrophils, eosinophils (blood or sputum), eosinophil cationic protein (ECP) (blood), interleukin 8 (IL(8)) (blood) and leukotriene E4 (LTE(4)) (urine) were high in the three groups (P>0.05). We demonstrated an association between the onset of exacerbation and the severity of obstruction (FEV(1)) (r=-0.360; P=0.037), eosinophils in sputum (r=-0.399; P=0.029), albumin (r=-0.442; P=0.013), and IL(8) in sputum (r=0.357; P=0.038). CONCLUSIONS The results suggest a rapid inflammatory response, both neutrophilic and eosinophilic, in the asthmatic exacerbation. However, the swelling in the bronchi may play an important role in the initial inflammatory response in the exacerbations depending of time of onset.

Sources of Calcium for the Contraction Induced by Various Agonists in Trachealis Muscle from Normal and Sensitized Guinea Pigs

Active sensitization of guinea pigs resulted in an increase in the responsiveness and sensitivity of tracheal strips to CaCl2 in K+-depolarized tissue (Emax 0.81 +/- 0.22 g/mm2 and pD2 2.35 +/- 0.10 in normal vs. 0.98 +/- 0.01 g/mm2 and 3.10 +/- 0.08 in sensitized tissue; p less than 0.05), KCl (Emax 0.62 +/- 0.08 g/mm2 and pD2 1.71 +/- 0.03 in normal vs. 0.91 +/- 0.04 g/mm2 and 2.00 +/- 0.01 in sensitized tissue; p less than 0.05) and histamine (Emax 0.70 +/- 0.06 g/mm2 and pD2 5.08 +/- 0.06 in normal vs. 0.94 +/- 0.09 g/mm2 and 5.80 +/- 0.16 in sensitized tissue; p less than 0.05) but not to caffeine 10 mM (20 degrees C, indomethacin 2.8 microM). Generation of responses to these agonists in nonsensitized tissues bathed in a Ca2+-free medium resulted in the abolition of KCl-induced contraction and partial inhibition of the responses to histamine (60% inhibition) and caffeine (40% inhibition). The contraction of sensitized tracheal strips in response to histamine in 0 calcium was greater than that obtained in nonsensitized tissues (0.48 +/- 0.02 g/mm2 vs. 0.28 +/- 0.04 g/mm2, respectively; p less than 0.05). The caffeine-induced contraction of sensitized tracheae was independent of extracellular calcium. These results suggest that a greater calcium entry and/or intracellular calcium release may be an alteration underlying hyperreactivity of sensitized tissues to spasmogens.