Cough Reflex Testing With Inhaled Capsaicin and TRPV1 Activation in Asthma and Comorbid Conditions

Se ha constatado en el asma la presencia de un tono parasimpático elevado que induce broncoconstricción e inflamación neurogénica en la vía aérea. Estas anomalías podrían jugar un papel primordial en la patogenia de la enfermedad. El receptor de vanilloid 1 (TRPV1) centraliza el control de todas las señales neurogénicas proinflamatorias. Es un receptor pulmonar sensible al daño y transmite toda la información del mismo al sistema nervioso central induciendo la liberación de diversos neuropépticos proinflamatorios a nivel de las terminaciones periféricas. La provocación con capsaicina inhalada, un agonista exógeno del receptor TRPV1, ha sido extensamente utilizada para cuantificar el reflejo de la tos. Sin embargo, su inhalación también se asocia con broncoconstricción parasimpática, hipersecreción mucosa, vasodilatación y disnea. Por tanto, es esperable que esta técnica podría potencialmente también tener otras aplicaciones en el estudio del asma y sus co-morbilidades causantes de tos, como son la rinitis o el reflujo gastroesofágico. Por tanto, además del papel en el estudio de esta reactividad sensorial de la vía aérea, se revisarán también otras posibles aplicaciones (AU)

A high parasympathetic tone leading to bronchoconstriction and neurogenic inflammation is thought to have a major role in the pathogenesis of asthma. Transient receptor potential vanilloid 1 (TRPV1) is the hub of almost all neuronal inflammatory signaling pathways. A critical determinant of neurogenic inflammation, TRPV1 functions as a sensor for detecting irritants in the lung by transmitting noxious stimuli to the central nervous system and inducing the release of a variety of proinflammatory neuropeptides at the peripheral terminals. Challenge with inhaled capsaicin, an exogenous agonist of TRPV1, has been used to measure the sensitivity of the cough reflex. However, inhalation of capsaicin is also associated with parasympathetic bronchoconstriction, mucus hypersecretion, vasodilatation, and the sensation of dyspnea. Therefore, inhaled capsaicin challenge is expected to have other potential applications in asthma and comorbid conditions, such as rhinitis and gastroesophageal reflux disease, both of which produce cough. Capsaicin challenge has established itself as a useful objective method for evaluating airway hypersensitivity; however, it is potentially valuable in many other situations, which will be reviewed in this paper (AU)

Increased lung neutrophil apoptosis and inflammation resolution in nonresponding pneumonia.

Neutrophil activation state and its relationship with an inflammatory environment in community-acquired pneumonia (CAP) remain insufficiently elucidated. We aimed to evaluate the neutrophil apoptosis and cytokine pattern in CAP patients after 72 h of treatment, and their impact on infection resolution. Apoptosis of blood and bronchoalveolar lavage (BAL) neutrophils was measured in nonresponding CAP (NCAP), in responding CAP (blood only) and in patients without infection (control). Pro-inflammatory (interleukin (IL)-6, IL-8) and anti-inflammatory (IL-10) cytokines were measured. Main outcomes were clinical stability and days of hospitalisation. Basal neutrophil apoptosis was higher in the BAL and blood of NCAP, whereas spontaneous apoptosis (after 24 h culture) was lower. Cytokines in NCAP were higher than in responding CAP and control: IL-6 was increased in BAL and blood, IL-8 in BAL and IL-10 in blood. An increased basal apoptosis (≥20%) in BAL of NCAP was associated with lower systemic IL-10 (p<0.01), earlier clinical stability (p=0.05) and shorter hospital stay (p=0.02). A significant correlation was found for systemic IL-6 and IL-10 with days to reach stability and length of stay. After 72 h of treatment, an increased basal alveolar neutrophil apoptosis might contribute to downregulation of inflammation and to faster clinical stability.

Relationship between the characteristics of hospitalised acute asthma patients and the severity of their asthma. A case-control study

Background: The EAGLE Project database was analysed to assess the characteristics of patients with severe asthma (SA) who required hospitalisation as a result of an acute episode during the period 1994–2004, and the relationship with asthma severity. Methods: A total of 2593 clinical records corresponding to an equal number of patients hospitalised for acute asthma (15–69 years), with sufficient information to characterize their asthma severity in agreement with GINA criteria were identified (727 patients with SA compared with 1866 patients with non-severe asthma). Results: Patients with SA were older, displayed a greater predominance of female asthmatics, lower antecedents of atopy, and a higher frequency of previous hospitalisations compared with non-severe asthmatics (86.1% vs. 50.5%, p ≤ 0.01). Additionally, SA patients showed more severe exacerbations characterized by acidosis, significant spirometric deterioration, greater length of hospital stay (9.4 days vs. 7.0 days), as well as a higher frequency of intubation (16.8% vs. 2.1%), intensive care unit admission (11.3% vs. 4.9%), cardiopulmonary arrest (5.5% vs. 1.3%), and asthma deaths (2.1% vs. 0.4%) (all p ≤ 0.01) compared with non-severe patients. Conclusions: This study suggests that SA patients have greater morbidity and a disproportionate need for health care as a result of more severe exacerbations. However, non-severe asthmatics can also still present acute severe episodes (although with a lower frequency) with risk of life (AU)

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Relationship between the characteristics of hospitalised acute asthma patients and the severity of their asthma. A case-control study.

BACKGROUND: The EAGLE project database was analysed to assess the characteristics of patients with severe (SA) who required hospitalisation as a result of an acute episode during the period 1994-2004, and the relationship with asthma severity. METHODS: A total od 2593 clinical records corresponding to an equal number of patients hospitalised for acute asthma (15-69 years), with sufficient information to characterize their asthma severity in agreement with GNA criteria were identified (727 patients with SA compared with 1866 patients with non-severe asthma). RESULTS: Patients with SA were older, displayed a greater predominance of female asthmatics, lower antecedents of atopy, and a higher frequency of previous hospitalisations compared with non-severe asthmatics (86.1% vs. 50.5%, p< or = 0.01). Additionally, SA patients showed more severe exacerbations characterized by acidosis, significant spirometric deterioration, greater length of hospital stay (9.4 days vs. 7.0 days), as well as a higher frequency of intubation (16.8% vs. 2.1%), intensive care unit admission (11.3% vs.4.9%), cardiopulmonary arrest (5.5% vs. 1.3%), and asthma deaths (2.1% vs. 0.4%) (all < or = 0.01) compared wit non-severe patients. CONCLUSIONS: This study suggests that SA patients have greater morbidity and a disproportionate need for health care as a result of more severe exacerbations. However, non-severe asthmatics can also still present acute severe episodes (although with a lower frequency) with risk of life.

[Does experience influence perception of dyspnea?]. / Influye la experiencia en la percepción de disnea?

OBJECTIVE: The perception of somatic sensations like dyspnea can be influenced by such factors as an individual s personality, experiences, or ability to adapt to stimuli. Our aim was to determine whether the perception of acute bronchoconstriction is different for patients with asthma and patients who have never experienced an episode of airway obstruction. PATIENTS AND METHOD: We studied 2 groups of patients. The first consisted of 24 subjects with intermittent rhinitis and asthma (10 females and 14 males) with a mean (SD) age of 25 (7) years. All reported not feeling dyspnea at rest on a Borg scale. The second group consisted of 24 subjects who only had rhinitis but no lung disease (no episode of asthma) or dyspnea at rest (12 females and 12 males) with a mean age of 27 (6) years. There were no significant differences between the groups with regard to sex, smoking, economic or educational level, anxiety (determined by the trait portion of the State-Trait Anxiety Inventory), depression (Beck Depression Inventory), or spirometric parameters. All took a histamine bronchial provocation test in which the patient assessed dyspnea on a modified Borg scale after each histamine dose. The provocation dose needed to produce a 20% decrease (PD20) in forced expiratory volume in the first second (FEV1) was calculated. We also recorded dyspnea perception score when FEV1 fell 5%, 10%, 15%, and 20%. RESULTS: No dyspnea was perceived at PS20 by 12.5% of the asthmatics and by 45% of nonasthmatics (P< .0001). The mean PS20 was 2.4 (2.1) (range, 0-7) in the first group and 0.37 (0.48) (range, 0-3) in the second (P< .0001). More asthma patients than nonasthmatics perceived dyspnea at all degrees of bronchial obstruction. PD20 was different in the 2 groups (1.6 [2] vs 6.03 [5] for the first and second groups, respectively; P< .003), but there was no significant relation between PD20 and PS20 (Spearman s correlation coefficient, 0.19; P= .221). CONCLUSION: Our findings support the hypothesis that appropriate perception of dyspnea is grounded in prior experience and learning.

¿Influye la experiencia en la percepción de disnea? / Does Experience Influence Perception of Dyspnea?

Objetivo: En la percepción de las sensaciones somáticas, como la disnea, pueden influir factores tales como la propia personalidad del individuo, su experiencia previa o su capacidad de adaptación a los estímulos. El objetivo del presente estudio ha sido conocer si los pacientes con asma perciben una situación de broncoconstricción aguda de forma diferente de los pacientes que nunca han sufrido un episodio previo de obstrucción de la vía aérea. Pacientes y método: Estudiamos 2 grupos de pacientes. El primero estaba formado por 24 sujetos con rinitis y asma intermitente (10 mujeres y 14 varones, con una edad media ± desviación estándar de 25 ± 7 años), que no referían sentir disnea basal en la escala de Borg. El segundo lo formaron 24 pacientes con rinitis sola, sin enfermedad pulmonar (nunca habían sufrido un episodio de asma) ni disnea basal (12 mujeres y 12 varones, edad media de 27 ± 6 años). No había diferencias significativas entre los grupos en cuanto a edad, sexo, porcentaje de fumadores, nivel económico y educativo, ansiedad ­determinada por el State-Trait Anxiety Inventory, versión Rasgo (STAI-R)­, depresión (Beck) ni parámetros espirométricos. A todos ellos se les realizó una prueba de broncoprovocación con histamina midiendo la disnea experimentada tras cada dosis del fármaco en una escala modificada de Borg. Se calculó la PD20, es decir, la dosis de agente broncoconstrictor capaz de producir un descenso del 20% del valor inicial del volumen espiratorio forzado en el primer segundo (FEV1), así como la percepción de disnea con una caída del FEV1 del 5, el 10, el 15 y el 20% (PS5, PS10, PS15 y PS20, respectivamente). Resultados: No percibió disnea con el descenso del 20% en el FEV1 el 12,5% de los pacientes con asma, frente a un 45% de las personas no asmáticas (p < 0,0001). La media de la PS20 en el primer grupo fue de 2,4 ± 2,1 (rango: 0-7) y en el segundo de 0,37 ± 0,48 (rango: 0-3) (p < 0,0001). En todos los grados de obstrucción bronquial la disnea percibida por los pacientes con asma fue mayor. La PD20 fue diferente en ambos grupos (1,6 ± 2 frente a 6,03 ± 5; p < 0,003), pero no hubo relación significativa entre la PD20 y la PS20 (coeficiente de correlación de Spearman: 0,19, p = 0,221). Conclusión: Nuestros datos apoyan la hipótesis de que la adecuada percepción de la disnea se fundamenta en aspectos como la experiencia previa y el aprendizaje

Objective: The perception of somatic sensations like dyspnea can be influenced by such factors as an individual´s personality, experiences, or ability to adapt to stimuli. Our aim was to determine whether the perception of acute bronchoconstriction is different for patients with asthma and patients who have never experienced an episode of airway obstruction. Patients and method: We studied 2 groups of patients. The first consisted of 24 subjects with intermittent rhinitis and asthma (10 females and 14 males) with a mean (SD) age of 25 (7) years. All reported not feeling dyspnea at rest on a Borg scale. The second group consisted of 24 subjects who only had rhinitis but no lung disease (no episode of asthma) or dyspnea at rest (12 females and 12 males) with a mean age of 27 (6) years. There were no significant differences between the groups with regard to sex, smoking, economic or educational level, anxiety (determined by the trait portion of the State-Trait Anxiety Inventory), depression (Beck Depression Inventory), or spirometric parameters. All took a histamine bronchial provocation test in which the patient assessed dyspnea on a modified Borg scale after each histamine dose. The provocation dose needed to produce a 20% decrease (PD20) in forced expiratory volume in the first second (FEV1) was calculated. We also recorded dyspnea perception score when FEV1 fell 5%, 10%, 15%, and 20%. Results: No dyspnea was perceived at PS20 by 12.5% of the asthmatics and by 45% of nonasthmatics (P<.0001). The mean PS20 was 2.4 (2.1) (range, 0-7) in the first group and 0.37 (0.48) (range, 0-3) in the second (P<.0001). More asthma patients than nonasthmatics perceived dyspnea at all degrees of bronchial obstruction. PD20 was different in the 2 groups (1.6 [2] vs 6.03 [5] for the first and second groups, respectively; P<.003), but there was no significant relation between PD20 and PS20 (Spearman´s correlation coefficient, 0.19; P=.221). Conclusion: Our findings support the hypothesis that appropriate perception of dyspnea is grounded in prior experience and learning

[Evolution over time in over perceivers of dyspnea in asthma]. / Evolución temporal de la percepción exagerada de disnea en los pacientes con asma.

OBJECTIVE: In previous studies we identified a subgroup of patients whose perception of breathlessness was exaggerated during acute bronchoconstriction and who were termed "over perceivers" or "hyperperceivers". In this study we aimed to determine whether such over perception is sporadic or stable over time. We also examined whether there is an association between over perception of dyspnea and hyperventilation syndrome. PATIENTS AND METHODS: The subjects were 22 stable asthmatics (11 men, 11 women) who had been over perceivers of dyspnea in a study 9 years earlier. After a medical history was taken, a patient performed forced spirometry and a severity classification was made according to the criteria of the Global Initiative for Asthma (GINA). A bronchial histamine challenge was then administered to measure dose-related perception of dyspnea on a Borg scale, according to a procedure that was similar to the one used 9 years earlier by the same investigator. The patients were also asked for a subjective assessment of the severity of their asthma (scale, 0-10) and to respond to items on the Nijmegen hyperventilation questionnaire and the trait form of the State-Trait Anxiety Inventory. RESULTS: The overall perception of severity of disease, level of anxiety, and perception of dyspnea at rest were lower after 9 years (P<.001). No change was observed in bronchial hyperresponsiveness (dose of inhaled histamine required to provoke a 20% decline in forced expiratory volume in the first second [FEV1]-PD20) or objective parameters of severity (FEV1 and GINA classification). Fourteen asthmatics (64%) were still over perceivers and the other patients had changed: 6 were normal perceivers and 2 were "poor perceivers". Only subjective perception of disease severity improved for the patients who were still over perceivers; the other patients, on the other hand, showed improvements in subjective assessments, objective ones (except PD20), and anxiety. Finally, those who remained over perceivers had higher scores for anxiety (24 vs 15; P<.05) and hyperventilation (18 vs 13; P= not significant). CONCLUSIONS: Most over perceivers of dyspnea remain so over the years and this trait is related to anxiety. We have been unable to demonstrate an association with hyperventilation syndrome.

Evolución temporal de la percepción exagerada de disnea en los pacientes con asma / Evolution over time in over perceivers of dyspnea in asthma

Objetivo: En investigaciones previas para estudiar la percepción de disnea de los asmáticos durante la broncoconstricción aguda, encontramos un subgrupo de pacientes que presentaban una percepción exagerada (hiperperceptores). En el presente trabajo hemos querido comprobar si esta alteración perceptiva es un fenómeno esporádico o mantenido en el tiempo. Asimismo nos planteamos conocer si existe una asociación entre la hiperpercepción de la disnea y el síndrome de hiperventilación. Pacientes y métodos: Se incluyó en el estudio a 22 asmáticos estables que en un estudio realizado 9 años antes se habían mostrado hiperperceptores de disnea (11 varones y 11 mujeres). Tras una espirometría forzada y una entrevista clínica, se les clasificó en su categoría de gravedad de asma ­GINA (Global Initiative for Asthma)­. A continuación se les sometió a una prueba de provocación bronquial con histamina para medir la disnea percibida con cada dosis en una escala de Borg (procedimiento similar al empleado 9 años antes por el mismo investigador). Además se les pidió una valoración subjetiva de la gravedad de su asma (escala de 0-10) y que rellenaran el cuestionario Nijmegen de hiperventilación y el STAI-R (State-Trait Anxiety Inventory) de ansiedad. Resultados: Globalmente, transcurridos 9 años, se han reducido (p < 0,001) la percepción de gravedad del asma, la ansiedad y la disnea basal. No se observaron cambios en el grado de hiperrespuesta bronquial (PD20: concentración de histamina capaz de provocar un descenso del volumen espiratorio forzado en el primer segundo del 20%) ni en parámetros objetivos de gravedad (volumen espiratorio forzado en el primer segundo y GINA). Catorce asmáticos seguían siendo hiperperceptores (64%) y en el resto había cambiado la percepción de la disnea: 6 normoperceptores y 2 hipoperceptores. En el grupo que seguía siendo hiperperceptor sólo mejoró significativamente la percepción subjetiva de gravedad; en cambio, en el grupo restante mejoraron la enfermedad subjetiva y objetivamente (excepto la PD20) y la ansiedad. Por último, los que continuaban siendo hiperperceptores puntuaron más alto en los cuestionarios de ansiedad (24 frente a 15; p < 0,05) e hiperventilación (18 frente a 13; p = no significativa). Conclusiones: La mayoría de hiperperceptores de disnea se mantienen así con el paso de los años, lo cual está relacionado con la ansiedad (no hemos podido demostrar su asociación con el síndrome de hiperventilación)

Objective: In previous studies we identified a subgroup of patients whose perception of breathlessness was exaggerated during acute bronchoconstriction and who were termed "over perceivers" or "hyperperceivers". In this study we aimed to determine whether such over perception is sporadic or stable over time. We also examined whether there is an association between over perception of dyspnea and hyperventilation syndrome. Patients and methods: The subjects were 22 stable asthmatics (11 men, 11 women) who had been over perceivers of dyspnea in a study 9 years earlier. After a medical history was taken, a patient performed forced spirometry and a severity classification was made according to the criteria of the Global Initiative for Asthma (GINA). A bronchial histamine challenge was then administered to measure dose-related perception of dyspnea on a Borg scale, according to a procedure that was similar to the one used 9 years earlier by the same investigator. The patients were also asked for a subjective assessment of the severity of their asthma (scale, 0-10) and to respond to items on the Nijmegen hyperventilation questionnaire and the trait form of the State-Trait Anxiety Inventory. Results: The overall perception of severity of disease, level of anxiety, and perception of dyspnea at rest were lower after 9 years (P<.001). No change was observed in bronchial hyperresponsiveness (dose of inhaled histamine required to provoke a 20% decline in forced expiratory volume in the first second [FEV1]-PD20) or objective parameters of severity (FEV1 and GINA classification). Fourteen asthmatics (64%) were still over perceivers and the other patients had changed: 6 were normal perceivers and 2 were "poor perceivers". Only subjective perception of disease severity improved for the patients who were still over perceivers; the other patients, on the other hand, showed improvements in subjective assessments, objective ones (except PD20), and anxiety. Finally, those who remained over perceivers had higher scores for anxiety (24 vs 15; P<.05) and hyperventilation (18 vs 13; P= not significant). Conclusions: Most over perceivers of dyspnea remain so over the years and this trait is related to anxiety. We have been unable to demonstrate an association with hyperventilation syndrome

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.

[Agreement in asthmatics' perception of dyspnea during acute and chronic obstruction]. / Concordancia entre la percepción de disnea del asmático durante la obstrucción aguda y crónica.

OBJECTIVE: Three types of asthmatic patients can be identified during periods of clinical stability: "poor perceivers," "normal perceivers," and "over perceivers." When asthmatics undergo bronchial challenge in the laboratory, the same distinctions in type of perception can be observed. The aim of the present study was to determine the level of agreement between the 2 situations. PATIENTS AND METHODS: A total of 93 patients with persistent moderate asthma (36 men and 57 women; mean age 40 years) were studied. We asked them to assess their dyspnea on a modified Borg scale when stable and after each histamine dose in a bronchial provocation test. When a patient's Borg scale assessment in stable situation was below the 25th percentile, that patient was classified as a poor perceiver. Patients were considered over perceivers if their score in stable situation was in the 75th percentile. Others were labeled normal perceivers. Type of perception during acute bronchoconstriction was defined in function of the change in Borg assessment once forced expiratory volume in the first second had decreased 20%: poor perceivers were those whose change in Borg assessment was in the 25th percentile, over perceivers were in the 75th percentile, and normal perceivers in the middle percentiles. RESULTS: In stable situation, 23 patients were poor perceivers, 58 were normal perceivers, and 12 were over perceivers. During bronchoconstriction, there were 23 poor perceivers, 47 normal perceivers, and 23 over perceivers. Agreement was estimated by a kappa index of 0.0574 for poor perception, 0.1521 for over perception, and 0.3980 for normal perception. CONCLUSIONS: Asthmatics' perception of dyspnea during periods of stability and during acute bronchoconstriction are independent phenomena. It is therefore not possible to infer how a patient will perceive an asthmatic attack by evaluating only how he or she perceives breathlessness during stable periods.

Concordancia entre la percepción de disnea del asmático durante la obstrucción aguda y crónica / Agreement in asthmatics' perception of dyspnea during acute and chronic obstruction

Objetivo: Durante la estabilidad clínica se pueden distinguir 3 tipos de asmáticos: hipoperceptores, normoperceptores e hiperperceptores. Cuando a esos mismos pacientes se les provoca una broncoconstricción aguda, también existen hipo, normo e hiperperceptores de disnea. El objetivo del presente trabajo ha sido comprobar la concordancia entre ambas situaciones. Pacientes y métodos: Se ha estudiado a 93 pacientes con asma persistente moderada (36 varones y 57 mujeres; edad media de 40 años). Se les pidió que estimaran su disnea (escala modificada de Borg) en situación de estabilidad y después de cada dosis de histamina en una prueba de broncoprovocación. Cuando la puntuación de Borg en situación estable era menor del percentil 25, se consideró hipoperceptor; si era superior al percentil 75, hiperperceptor, y normoperceptor al grupo restante. En función del cambio de disnea al descender un 20% el volumen espiratorio forzado en el primer segundo se distinguieron los perceptores agudos: hipoperceptores (cambio en Borg inferior al percentil 25), hiperperceptores (cambio superior al percentil 75) y normoperceptores (cambio entre los percentiles 25 y 75). Resultados: En situación estable 23 pacientes fueron hipoperceptores, 58 normoperceptores y 12 hiperperceptores, mientras que durante la broncoconstricción hubo 23 hipoperceptores, 47 normoperceptores y 23 hiperperceptores. El análisis de concordancia mostró un índice kappa de 0,0574 para la hipopercepción, de 0,1521 para la hiperpercepción y de 0,3980 para la normopercepción. Conclusiones: Las percepciones de disnea de los asmáticos en situación estable y durante una broncoconstricción aguda son fenómenos independientes. Por ello, no es posible inferir cómo un paciente va a percibir una crisis de asma valorando únicamente cómo percibe su enfermedad durante la estabilidad clínica

Objective: Three types of asthmatic patients can be identified during periods of clinical stability: "poor perceivers," "normal perceivers," and "over perceivers." When asthmatics undergo bronchial challenge in the laboratory, the same distinctions in type of perception can be observed. The aim of the present study was to determine the level of agreement between the 2 situations. Patients and Methods: A total of 93 patients with persistent moderate asthma (36 men and 57 women; mean age 40 years) were studied. We asked them to assess their dyspnea on a modified Borg scale when stable and after each histamine dose in a bronchial provocation test. When a patient's Borg scale assessment in stable situation was below the 25th percentile, that patient was classified as a poor perceiver. Patients were considered over perceivers if their score in stable situation was in the 75th percentile. Others were labeled normal perceivers. Type of perception during acute bronchoconstriction was defined in function of the change in Borg assessment once forced expiratory volume in the first second had decreased 20%: poor perceivers were those whose change in Borg assessment was in the 25th percentile, over perceivers were in the 75th percentile, and normal perceivers in the middle percentiles. Results: In stable situation, 23 patients were poor perceivers, 58 were normal perceivers, and 12 were over perceivers. During bronchoconstriction, there were 23 poor perceivers, 47 normal perceivers, and 23 over perceivers. Agreement was estimated by a kappa index of 0.0574 for poor perception, 0.1521 for over perception, and 0.3980 for normal perception. Conclusions: Asthmatics' perception of dyspnea during periods of stability and during acute bronchoconstriction are independent phenomena. It is therefore not possible to infer how a patient will perceive an asthmatic attack by evaluating only how he or she perceives breathlessness during stable periods

[Prevalence of hyperventilation syndrome in patients treated for asthma in a pulmonology clinic]. / Prevalencia del síndrome de hiperventilación en pacientes tratados por asma en una consulta de neumología.

OBJECTIVE: Although the presence of hyperventilation syndrome can affect the symptoms of patients with asthma, there is very little information available regarding its frequency in Spain. The aim of this study was to investigate the prevalence of hyperventilation syndrome in the asthmatic population treated as outpatients and establish its relationship with anxiety disorders. PATIENTS AND METHOD: We studied 157 consecutive asthmatic patients (61 men and 96 women; mean [SD] age, 45 [17] years; forced expiratory volume in the first second, 84% [21%] of the predicted value) treated in our outpatients clinic. The patients had stable disease with varying degrees of severity. After collecting demographic data and medical histories, we asked the patients to complete the Spanish versions of the Anxiety Sensitivity Index, the Asthma Symptom Checklist, and the Nijmegen questionnaire; in the latter test, a score of 23 or over was considered diagnostic for hyperventilation syndrome. Finally, patients were evaluated to determine whether they had suffered from panic disorder in the last 6 months (according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders). RESULTS: Hyperventilation syndrome was present in 57 asthmatic patients (36%) and panic disorder in 4 patients (2%). The majority of patients with hyperventilation syndrome were women (78% vs 51%; P=.001) and were older (49 vs 42; P=.01); they displayed more basal dyspnea (1.26 vs 0.89 on the Medical Research Council scale; P=.01), greater sensitivity to anxiety (P=.001), and went to the emergency room more often for exacerbations (P=.002). Patients with hyperventilation syndrome scored significantly higher on all subscales of the Asthma Symptoms Checklist. Finally, the variables introduced in the regression analysis (stepwise) to explain the score on the Nijmegen questionnaire (r(2)=0.57) were basal dyspnea and sensitivity to anxiety. CONCLUSIONS: Approximately one third of the asthmatic patients treated in a pulmonology clinic also present hyperventilation syndrome. This cannot be explained by comorbidity of asthma with panic disorder, and is only partly linked to the symptoms associated with hyperventilation that appear during an asthma attack.

Prevalencia del síndrome de hiperventilación en pacientes tratados por asma en una consulta de neumología / Prevalence of hyperventilation syndrome in patients treated for asthma in a pulmonology clinic

Objetivo: Aunque la presencia del síndrome de hiperventilación (SH) puede influir en los síntomas de los pacientes con asma, existe escasa información acerca de su frecuencia en nuestro medio. Nuestro objetivo ha sido investigar la prevalencia de SH entre la población asmática controlada ambulatoriamente y establecer su relación con los trastornos de ansiedad. Pacientes y método: Con este propósito hemos estudiado a 157 asmáticos consecutivos (61 varones, 96 mujeres; edad media ± desviación estándar de 45 ± 17 años; volumen espiratorio forzado en el primer segundo: 84 ± 21%), controlados en nuestras consultas externas, en situación estable y con diferentes grados de gravedad. Tras recoger los datos demográficos y los relativos a su enfermedad, cumplimentaron las versiones españolas del Índice de Sensibilidad a la Ansiedad, el Listado de Síntomas durante un Ataque de Asma y el cuestionario Nijmegen; en este último, una puntuación de 23 o superior se consideró diagnóstica del SH. Finalmente, se valoró si habían presentado un trastorno de pánico en los 6 últimos meses (criterios de la cuarta edición del Manual diagnóstico y estadístico de los trastornos mentales). Resultados: Presentaron SH 57 asmáticos (36%) y trastorno de pánico, 4 (2%). Los pacientes con SH eran mayoritariamente mujeres (un 78 frente a un 51%; p = 0,001) y tenían más edad (49 frente a 42; p = 0,01), más disnea basal (1,26 en la escala del Medical Research Council frente a 0,89; p = 0,01), más sensibilidad a la ansiedad (p = 0,001) y acudían más veces a urgencias por agudizaciones (p = 0,002). Los pacientes con SH puntuaron significativamente más alto en todas las subescalas del Listado de Síntomas durante un Ataque de Asma. Por último, las variables introducidas en el análisis de regresión (pasos sucesivos) para explicar la puntuación en el cuestionario Nijmegen (r² = 0,57) fueron: disnea basal y sensibilidad a la ansiedad. Conclusiones: Aproximadamente un tercio de los asmáticos controlados en una consulta de neumología presentan además SH. Esto no puede explicarse por la comorbilidad asma-trastorno de pánico y tiene que ver sólo en parte con los síntomas relacionados con la hiperventilación que aparece durante un ataque de asma

Objective: Although the presence of hyperventilation syndrome can affect the symptoms of patients with asthma, there is very little information available regarding its frequency in Spain. The aim of this study was to investigate the prevalence of hyperventilation syndrome in the asthmatic population treated as outpatients and establish its relationship with anxiety disorders. Patients and method: We studied 157 consecutive asthmatic patients (61 men and 96 women; mean [SD] age, 45 [17] years; forced expiratory volume in the first second, 84% [21%] of the predicted value) treated in our outpatients clinic. The patients had stable disease with varying degrees of severity. After collecting demographic data and medical histories, we asked the patients to complete the Spanish versions of the Anxiety Sensitivity Index, the Asthma Symptom Checklist, and the Nijmegen questionnaire; in the latter test, a score of 23 or over was considered diagnostic for hyperventilation syndrome. Finally, patients were evaluated to determine whether they had suffered from panic disorder in the last 6 months (according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders). Results: Hyperventilation syndrome was present in 57 asthmatic patients (36%) and panic disorder in 4 patients (2%). The majority of patients with hyperventilation syndrome were women (78% vs 51%; P=.001) and were older (49 vs 42; P=.01); they displayed more basal dyspnea (1.26 vs 0.89 on the Medical Research Council scale; P=.01), greater sensitivity to anxiety (P=.001), and went to the emergency room more often for exacerbations (P=.002). Patients with hyperventilation syndrome scored significantly higher on all subscales of the Asthma Symptoms Checklist. Finally, the variables introduced in the regression analysis (stepwise) to explain the score on the Nijmegen questionnaire (r²=0.57) were basal dyspnea and sensitivity to anxiety. Conclusions: Approximately one third of the asthmatic patients treated in a pulmonology clinic also present hyperventilation syndrome. This cannot be explained by comorbidity of asthma with panic disorder, and is only partly linked to the symptoms associated with hyperventilation that appear during an asthma attack

Prevalencia de la desnutrición en pacientes ambulatorios con enfermedad pulmonar obstructiva crónica estable / Prevalence of malnutrition in outpatients with stable chronic obstructive pulmonary disease

OBJETIVO: Determinar la prevalencia de la desnutrición en pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable, controlados en una consulta especializada de neumología. MATERIAL Y MÉTODO: Se realizó un estudio prospectivo y consecutivo en pacientes con EPOC estable controlados de forma ambulatoria. Para valorar el estado nutricional empleamos diversos parámetros antropométricos. Se definió desnutrición global (bajo peso corporal) como la presencia de un índice de masa corporal inferior al percentil 25 del valor de referencia. Para valorar el compartimiento proteico muscular se determinó el área muscular del brazo y se definió la depleción muscular como un valor de área muscular del brazo igual o inferior al percentil 25.Como valoración de la proteína visceral se midieron las concentraciones plasmáticas de albúmina y transferrina. El compartimiento graso se estudió mediante la determinación de la grasa corporal total. Un valor de ésta igual o inferior al percentil 25 se utilizó como criterio de desnutrición calórica. Se realizaron a todos los pacientes espirometría y gasometría arterial en reposo. RESULTADOS: Se incluyó en el estudio a 178 pacientes -una mujer (0,6 por ciento) y 177 varones (99,4 por ciento)-, con una edad media de 69 ñ 9 años. Las prevalencias de bajo peso corporal, desnutrición proteica, muscular o visceral y depleción grasa fueron del 19,1, el 47,2, el 17,4 y el 19,1 por ciento, respectivamente. Entre los pacientes con normopeso, el 62,9 por ciento presentaba pérdida de masa muscular. La proporción de casos con índice de masa corporal igual o menor del percentil 25 o área muscular del brazo igual o inferior al percentil 25 aumentó de forma significativa a medida que empeoraba el grado de obstrucción bronquial (p < 0,001 y p = 0,015, respectivamente). No obstante, hasta un 35,7 por ciento de los pacientes con EPOC leve también mostraron depleción proteica muscular. CONCLUSIONES: La desnutrición en pacientes con EPOC estable es un problema frecuente, que aumenta con la gravedad de la enfermedad. La depleción afecta tanto al compartimiento graso como al proteico muscular y visceral. No obstante, existe un cierto efecto preferencial sobre la pérdida de masa muscular. Una proporción significativa de pacientes con normopeso también sufre desnutrición proteica muscular. Pese a que las alteraciones en la composición corporal son frecuentes, nuestros resultados reflejan una prevalencia de bajo peso corporal menor que la de diversas series publicadas en países de nuestro entorno social y económico (AU)

[Prevalence of malnutrition in outpatients with stable chronic obstructive pulmonary disease]. / Prevalencia de la desnutrición en pacientes ambulatorios con enfermedad pulmonar obstructiva crónica estable.

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.

Duration of length of stay in pneumonia: influence of clinical factors and hospital type.

Length of stay (LOS) in hospital for community-acquired pneumonia depends on the characteristics of the patient and hospital. The present study sought to identify these variables within the first 24 h of hospitalisation. Patients hospitalised for pneumonia in four hospitals (one teaching and three general hospitals) had their data analysed by univariate and multivariate statististics. The variables entered were LOS, demographical characteristics, referral source, comorbidity, initial severity of illness, laboratory analyses, initial radiograph findings and antibiotic treatment regimens. The study sample included 425 patients. The overall mortality was 8.2% and the median LOS was 9 days. Using LOS as a dependent variable, three multivariate linear regression analyses were performed with: 1) the whole cohort; 2) the low-risk classes (categories I and II of Fine); and 3) the high-risk classes (categories III, IV and V of Fine). The mathematical model identified hypoxemia, low diastolic pressure, pleural effusion, multi-lobe involvement and hypoalbuminaemia as associated with longer stays in risk classes III-V, while in the low-risk patients (I-II) only hypoxemia and pleural effusion appeared in the equation. Following adjustment for these clinical variables, the LOS remained lower in some hospitals. Several independent clinical factors increased the pneumonia-associated length of stay with significant differences between hospitals. Hypoxemia and pleural effusions were the predictive variables of length of stay in low-risk patients and, additionally, diastolic blood pressure, multi-lobe involvement and hypoalbuminaemia were significant in the higher-risk classes III-V.

[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.