Asociación entre colonización-infección crónica por Pseudomonas aeruginosa e hiperreactividad bronquial en pacientes con fibrosis quística / Association Between Chronic Colonization or Infection With Pseudomonas aeruginosa and Bronchial hyperreactivity in patients with cystic fibrosis

Objetivo: La hiperreactividad bronquial (HRB) es un hallazgo común en la fibrosis quística (FQ), que no se ha relacionado de forma concluyente con la atopia. El objetivo del estudio ha sido investigar la relación existente entre la colonización-infección crónica por Pseudomonas aeruginosa y la HRB en un grupo de pacientes con FQ. Pacientes y métodos: Se realizó la prueba de broncoprovocación inespecífica con histamina a un grupo de 32 pacientes con FQ cuya edad media ± desviación estándar era de 11,25 ± 3,7 años. Además se investigó en estos pacientes la existencia de atopia y colonización-infección crónica por P. aeruginosa. Resultados: De los 32 pacientes estudiados, se encontró HRB en 9 (28,1%), cuya situación clínica era significativamente peor. Estos 9 pacientes con HRB presentaron todos colonización-infección crónica por P. aeruginosa. Tenían atopia 17 pacientes (53,1%) de la muestra estudiada, pero sólo 3 (33,3%) de los 9 con HRB. La HRB se asoció significativamente con la colonización-infección crónica por P. aeruginosa (p < 0,001), pero no con la atopia (p = 0,12). Entre los pacientes sin atopia, la colonización se asoció significativamente con HRB (p = 0,017). Además, en el grupo de pacientes con función pulmonar normal (volumen espiratorio forzado en el primer segundo ≥ 80%) esta asociación fue también significativa (p = 0,044), mientras que la asociación entre HRB y atopia no lo fue (p = 0,11). Conclusiones: Los resultados del presente estudio indican que en pacientes con FQ la HRB podría estar relacionada con la colonización-infección crónica por P. aeruginosa, que podría ser un factor de riesgo de HRB más importante que la atopia

Objective: In patients with cystic fibrosis, bronchial hyperreactivity is a common finding that has not been conclusively associated with atopy. The objective of the present study was to determine the relationship between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in a group of patients with cystic fibrosis. Patients and methods: A nonspecific histamine bronchial provocation test was administered to a group of 32 cystic fibrosis patients with a mean (SD) age of 11.25 (3.7) years. The presence of atopy and of chronic colonization or infection with P aeruginosa was also studied. Results: Nine of the 32 patients (28.1%) studied showed bronchial hyperreactivity. The clinical status of these 9 patients was significantly worse and all were colonized or infected with P aeruginosa. Atopy was present in 17 of the 32 patients (53.1%) in the study group, but in only 3 of the 9 patients (33.3%) with bronchial hyperreactivity. Bronchial hyperreactivity was significantly associated with colonization or infection with P aeruginosa (P<.001), but not with atopy (P=.12). In the patients without atopy, colonization was significantly associated with bronchial hyperreactivity (P=.017). In the group with normal lung function (forced expiratory volume in 1 second ≥80%) this association was also significant (P=.044), while the association between bronchial hyperreactivity and atopy was not (P=.11). Conclusions: The results of the present study suggest that in patients with cystic fibrosis, bronchial hyperreactivity may be associated with colonization or infection with P aeruginosa, and that this may be a more important risk factor for bronchial hyperreactivity than atopy

El tratamiento según la guía de la Global Initiative for Asthma (GINA) reduce la morbimortalidad de los pacientes con asma de riesgo vital / Management according to the global initiative for asthma guidelines of patients with near-fatal asthma reduces morbidity and mortality

Objetivo: Valorar el efecto de un adecuado tratamiento ambulatorio, de acuerdo con las recomendaciones de la guía de la Global Initiative for Asthma (GINA), en la evolución a largo plazo del asma de riesgo vital (ARV). Pacientes y métodos: Durante una media de 49 meses se realizó el seguimiento de 53 pacientes que habían sobrevivido a una crisis de ARV y que se trataron de acuerdo con las recomendaciones de la GINA (grupo de intervención). Se obtuvieron datos clínicos y espirométricos retrospectivos y prospectivos (antes y después del ataque de ARV, respectivamente) y se compararon con los de 40 pacientes con ARV que no fueron tratados según las recomendaciones de la GINA (grupo control histórico) y cuyo seguimiento medio fue de 51 meses. Resultados: No se registraron fallecimientos en el grupo de intervención, mientras que en el grupo control murieron 6 pacientes (15%) (p = 0,005). Los nuevos ataques de ARV fueron significativamente menores (p < 0,001) en el grupo de intervención, con una media ± desviación estándar de 0,17 ± 0,61, frente a 1,6 ± 1 en el grupo control. En el grupo de intervención las visitas a urgencias descendieron de 0,9 ± 1,8 a 0,3 ± 0,6 después de la crisis de ARV (p = 0,03), y los ingresos hospitalarios pasaron de 3,4 ± 5,1 a 0,5 ± 1,4 (p < 0,001); el recuento de eosinófilos en sangre periférica descendió de 390 ± 411 a 159 ± 121 células x 109/l (p = 0,01) y el volumen espiratorio forzado en el primer segundo aumentó del 68 ± 23% al 76 ± 20% (p = 0,006). Conclusiones: En los pacientes que han presentado una crisis de ARV el tratamiento siguiendo las recomendaciones de la GINA se asocia a un descenso de la morbilidad y la mortalidad del asma

Objective: To assess the effect of adequate outpatient care as defined by guidelines of the Global Initiative for Asthma (GINA) on the long-term outcome of near-fatal asthma. Patients and methods: Fifty-three patients who had experienced a near-fatal attack of asthma were treated according to the GINA guidelines and followed for a mean of 49 months (intervention group). Clinical and spirometric measurements corresponding to the periods before the attack (obtained retrospectively) and after the attack (obtained prospectively) were compared to measurements from 40 near-fatal asthma patients who had not been managed according to the GINA guidelines and who were followed for a mean of 51 months (historic control group). Results: There were no deaths in the intervention group and 6 deaths (15%) in the control group (P=.005). The mean (SD) number of new near-fatal asthma attacks was significantly lower in the intervention group (0.17 [0.61]) than in the control group (1.6 [1]) (P<.001). Emergency visits following a near-fatal asthma attack decreased from 0.9 (1.8) to 0.3 (0.6) in the intervention group and hospital admissions decreased from 3.4 (5.1) to 0.5 (1.4) (P<.001). Eosinophil count decreased from 390 (411) x l09 cells/L to 159 (121) x l09 cells/L (P=.01) and forced expiratory volume in 1 second increased from 68% (23%) of predicted to 76% (20%) (P=.006). Conclusions: Management according to the GINA guidelines of patients who had experienced a near-fatal asthma attack was associated with a decrease in asthma morbidity and mortality

Parietaria sublingual allergoid immunotherapy with a co-seasonal treatment schedule

Background: Sublingual immunotherapy (SLIT) with monomeric allergoid, given according to the standard scheme, resulted effective and safe. However, the achievement of a clinical benefit requires a long time. We thus performed this study using an administration protocol starting in the co-seasonal period with a 3-day build-up phase and lasting only 6 months, in order to obtain the above benefit in a shorter time. Methods and results: The study, prospective, randomised and controlled versus drug therapy, was conducted on 65 rhinitic and/or asthmatic patients allergic to Parietaria with or without other sensitisations. Twenty-four were allocated to 1,000 AU/week, 21 to 3,000 AU/week and 21 to drug therapy. They were treated from April to September 2006. At baseline, 3 and 6 months a Visual Analogue Scale (VAS) was performed to assess the patients' well-being. Drug consumption was evaluated by means of monthly diary cards. Bronchial reactivity was investigated at baseline and 6 months by methacholine challenge test. There was a greater VAS improvement in both the SLIT groups than in the controls after 6 months (p < 0.05). In patients taking 3,000 AU/week this was already evident after 3 months. There was a significant reduction in rescue medication consumption between 3 and 6 months (p < 0.05) in all three groups. The bronchial reactivity was reduced only in the SLIT groups (p < 0.001). No adverse events were observed. Conclusions: At 6 months the allergoid SLIT showed itself to be effective and safe. In addition the subjective clinical benefit was obtained in a more rapid period, i.e. 3 instead of 6 months, when a higher maintenance dose was administered

No disponible

Effect of lung volume maintenance during sleep in nocturnal asthma.

Previous studies have shown that lung volume decreases and airway resistance increases during sleep in patients with nocturnal asthma. To determine whether the fall in lung volume per se causes the overnight decrement in forced expiratory volume in 1 s (FEV1) and/or increase in bronchial responsiveness, we investigated the effect of preventing this nocturnal decrease in lung volume. The mean volume change on a baseline night was -16.3 +/- 1.6% from presleep values and on the volume maintenance night +7.1 +/- 3.0% (P = 0.0001). However, this maintenance of lung volume did not alter the overnight decrement in FEV1 (-29.6 +/- 5.2% baseline vs. -30.2 +/- 5.8% volume maintenance). Similarly, the increase in bronchial responsiveness was also unaltered from baseline to volume maintenance nights, with presleep provocative concentrations of methacholine producing a 20% decrement in FEV1 of 0.28 +/- 0.15 vs. 0.22 +/- 0.7 mg/ml, respectively, and postsleep values of 0.07 +/- 0.03 vs. 0.04 +/- 0.02 mg/ml, respectively. Thus the fall in lung volume during sleep in the nocturnal asthmatic patient is a result, not a cause, of the overnight worsening of lung function.

The effect of 2 weeks treatment with cetirizine on bronchial reactivity to methacholine in asthma.

1. We investigated the effect of 2 weeks therapy with oral cetirizine (10 mg twice daily) on methacholine bronchial reactivity in 14 asthmatics. All had bronchial hyperreactivity to methacholine on entry to the study, with a geometric mean cumulative PC20 of 0.83 mg ml-1 (range 0.1-3.61 mg ml-1) and eight were atopic on skin prick testing. 2. The study was placebo-controlled and in randomised order, with a minimum 1 month washout period between cetirizine and placebo study periods. Four methacholine challenges were performed in all, at the beginning and at the end of each study period. 3. No significant change in methacholine reactivity was found following 2 weeks therapy with cetrizine. The repeatability coefficient for the PC20 methacholine over 2 weeks was found to be 2.90 doubling dilutions for the placebo period and 1.73 doubling dilutions for the cetirizine period. The study had a 80% power at the 5% significance level (two-tailed) to detect a 1.16-doubling concentration change in methacholine reactivity. 4. We conclude that 2 weeks therapy with cetirizine has no significant effect on non-specific bronchial hyperreactivity.

Nasal disorders and anticholinergic therapy.

Treatment of patients with perennial rhinitis, common cold and watery nasal hypersecretion, is still unsatisfactory. As the glands are innervated by parasympathetic nerves we examined the effect of intranasal application of a parasympatholytic drug, ipratropium bromide. In the laboratory we have studied the effect, dosage and duration of ipratropium in normal subjects. These investigations showed a strong inhibition of the secretion from the nasal glands for more than 6 hours in a dosage regimen with no local or systemic adverse effects. We continued in a placebo-controlled clinical short term study and an open long term study on patients with perennial rhinitis. Furthermore we conducted a clinical trial in patients with common cold. We found an effect on watery hypersecretion in all these patient groups. Several laboratory and clinical studies have since confirmed our results. Ipratropium inhibits the reflectory watery secretion from the nasal glands, but does not change the basal secretion rate. The onset of action is rapid and the effect is prolonged. Long term treatment is safe and may possibly have a curative effect in some patients.

Increase in bronchial responsiveness to methacholine and late asthmatic response after the inhalation of ultrasonically nebulized distilled water.

We studied ten subjects who had an asthmatic response after the inhalation of ultrasonically nebulized distilled water and did not show any refractory period to repeated challenge with such water. The change in responsiveness to methacholine after inhalation of distilled water and the occurrence of any water-induced late asthmatic response were investigated on separate days. All of the tested subjects showed a significant increase in bronchial responsiveness to methacholine after prior stimulation with ultrasonically nebulized distilled water, which waned within two hours in eight of them. The other two subjects showed a progressive increase in responsiveness to methacholine, and they also had a further reduction in the caliber of the airways three to four hours after inhalation of distilled water. The late responses were less severe than the initial responses and lasted four to five hours. After the spontaneous recovery, no significant increase in responsiveness to methacholine was detected. Our results confirm previous observations on hyperresponsiveness induced by ultrasonically nebulized distilled water and demonstrate the occurrence of late reactions after inhalation of such water.

Interpretation of the variability of peak flow rates in chronic bronchitis.

Increased diurnal variation of expiratory flow rates has been documented in patients with chronic bronchitis, but this could be secondary to the disease process of bronchitis rather than an associated disease--namely, asthma. Peak expiratory flow was measured twice daily before and after inhalation of 200 micrograms salbutamol in 34 subjects with chronic bronchitis. The FEV1 ranged from 38% to 121% predicted. Diurnal variation (expressed as highest-lowest/highest (%)) was increased in 18 subjects, all but three of whom had airflow obstruction and an increase in methacholine airway responsiveness. There was only a weak correlation between diurnal variation and airway responsiveness (r = -0.54) or the severity of the airflow obstruction. This finding, together with the occurrence of an increase in diurnal variation without an increase in methacholine airway responsiveness in three subjects, suggests that the increased diurnal variation in chronic bronchitis may have a different underlying mechanism from that in asthma.

Nasal responsiveness to methacholine stimulation in allergic rhinitis patients.

We examined the nasal responsiveness to topical methacholine application in allergic rhinitis and non-allergic chronic rhinitis patients, and in control subjects. Methacholine responsiveness was significantly higher in allergic rhinitis patients than in non-allergic patients and control subjects. In perennial rhinitis, methacholine responsiveness correlated with the severity of daily nasal symptoms and those provoked by specific allergen challenge tests. Among nasal symptoms, hyper-rhinorrhoea was found to be closely related to methacholine responsiveness. As a result of these findings, the possibility of cholinergic hyper-reactivity in allergic rhinitis patients is discussed.

Recurrent pneumonia in children and its relationship to bronchial hyperreactivity.

To determine what conditions are most likely to cause persistent or recurrent pneumonia (PRP) in children, the records of 81 children referred to James Whitcomb Riley Hospital for Children for evaluation of PRP were reviewed. Twenty patients had an apparent underlying cause that predisposed them to PRP. Of the 61 remaining patients (mean age 3.8 years) without any apparent cause for PRP, 49% had a history of allergy or family history of asthma, 31% patients had a history of wheezing and 18% were wheezing during their initial visit. No patient had an elevated sweat chloride determination or immunoglobulin deficiency. Of the 12 patients who were able to be recalled for pulmonary function testing, three had airflow obstruction that responded to an inhaled bronchodilator (isoproterenol). Of the nine patients with normal function, eight responded to methacholine with a decrease from base line in the one-second forced expiratory volume of greater than 20%. In all, 92% of those tested had bronchial hyperreactivity. These results indicate that asthma is a common cause of PRP in children and that PRP may occur as the initial symptom even in the absence of wheezing.

Medical therapy for experimental hypotony.

Experimental hypotony was induced in rhesus monkeys by the following procedures: ciliochoroidal detachment, retinal detachment, or cyclodialysis. Two days later, at the time of greatest hypotony, 10% methacholine chloride was deposited in the cornea by iontophoresis, and 0.25% physostigmine salicylate ointment was applied topically to each eye. The intraocular pressure rose to normal levels in all eyes for eight to 24 hours. The peak rise in IOP occurred one to four hours after drug administration and was 7.2, 6.8, and 11.3 mm Hg higher than the pretreatment levels in eyes with ciliochoroidal detachment, retinal detachment, and cyclodialysis, respectively. In a group of normal eyes, this drug combination caused a transient 5.7 mm Hg fall in IOP. The mechanism of pressure elevation by methacholine and physostigmine probably is caused by stimulation of aqueous humor formation or reduced uveoscleral outflow, or both.

Asthma in a rural highland area of Papua New Guinea.

Asthma is uncommon in the rural areas of Papua, New Guinea. Since 1976 an increasing number of people in the Fore linguistic group of the Eastern Highlands have been reported to have acute dyspnea responding to bronchodilator tablets. A preliminary investigation was undertaken to determine if these people had asthma. Forty-six patients who had been given bronchodilator therapy during the previous two years were examined by history, physical examination, lung function, methacholine provocation, skin prick tests, and IgE measurement. Nineteen patients had asthma with increased bronchial reactivity--defined as a 20% fall in FEV, after less than 0.75 mg of methacholine, or a greater than 20% rise in FEV1 after orciprenaline aerosol--together with a history of intermittent breathlessness. Eighteen had irreversible chronic airflow obstruction, and in nine patients it was not possible to distinguish between asthma and irreversible airflow obstruction. All but two of the asthmatics were over the age of 20, their symptoms began between 2 and 8 years previously, all were atopic, and all had elevated serum IgE levels. Non had a prior history of rhinitis or eczema. No obvious change in the environment or life style was found to explain the recent onset of severe asthma in these people.

Drug-induced changes in airways obstruction reflected by forced expiratory flows and airway resistance measured with an oscillometric method using quiet breathing.

14 patients with partially reversible airways obstruction were studied with forced expiratory flows (FEV1, PEFR) and with airway resistance measured by an oscillometric method (Siregnost FD-5) before and after drug-induced changes in airways obstruction. 10 inhaled methacholine to induce bronchoconstriction, and 4 inhaled salbutamol and an additional dose of neosynephrine to induce bronchodilation. Intraindividual changes in resistance (Rosc) measured by the oscillometer with quiet breathing showed a fair significant correlation with changes in FEV1 (r = 0.54, p less than 0.05) and changes in PEFR measured by the Wright peak flow meter (r = 0.59, p less than 0.05). The present type of oscillator can be used for provocations starting from normal airway resistance but not for measures of treatment effects in markedly obstructive patients.

Analysis of the methacholine response in bronchial asthma.

The airway response to methacholine was measured in 27 asthmatics. Selected indices of airway response were measured at 5-, 10- and 20-minute intervals and at three concentrations of methacholine. The mean change from control was significant at all three concentrations and there were no significant differences between time intervals. High correlations were obtained between all indices of airway response to methacholine challenge.

The effect of atropine on acute antigen-mediated airway constriction in subjects with allergic asthma.

Exposure to antigen by inhalation challenge may produce airway constriction in patients with allergic asthma. To examine the role of reflex bronchoconstriction mediated by the vagus nerve in the antigen-induced airway response, we compared the responses of 6 asthmatic volunteers to inhaled ragweed antigen alone and to antigen given after pretreatment with atropine sulfate, a parasympathetic blocking agent. We found significant increases in airway resistance, limitation of parasympathetic blocking agent. We found significant increases in airway resistance, limitation of forced expiratory flow, increases in lung volumes, and alterations in the distribution of inspired gas after antigen was given. When subjects were pretreated with atropine, we found a mean increase in the 1-sec forced expired volume of 0.380 liter (P less than 0.025) and a mean increase in specific airway conductance of 0.067 sec-1-cm H2O-1 (P less than 0.005). Atropine pretreatment did not prevent the responses to antigen in our subjects. After atropine pretreatment subjects began the antigen challenge with better pulmonary function and at a given antigen dose maintained a better level of function compared to when antigen was given alone. Differences in the absolute level of pulmonary function between the two challenges became smaller with the administration of larger antigen doses. We conclude that reflex bronchospasm involving postganglionic efferent parasympathetic nerve pathways is not a major component of the response to inhaled antigen in human allergic asthma.

Preliminary studies of pharmacological antigonism of anaphylaxis in the horse.

Systemic anaphylaxis was induced in seven groups of ponies. Systemic hypotension, pulmonary hypotension, and apnea were observed in the control group. Suppression of anaphylaxis was achieved most efficiently with sodium meclofenamate followed by acetylsalicylic acid and diethylcarboamazine. Tripelennamine and methysergide reduced anaphylaxis minimally and burimamide not at all. The findings suggest that histamine and serotonin are of relatively low significance in equine anaphylaxis whereas kinins, prostaglandins and slow reacting substance may be more important.

A comparison of methacholine and histamine inhalations in asthmatics.

Bronchial provocation tests using aerosolized serially diluted histamine and methacholine were given to nearly 200 asthmatics. Results were usually reproducible for a given patient and corticosteroids did not influence the procedures. Those patients who could tolerate high doses of methacholine were statistically the least severe asthmatics as measured by their discharge dose of corticosteroids. Reaginmediated asthmatics could not tolerate the higher doses of histamine. These tests help delineate subgroups of asthmatics and may have clinical usefulness since, when combined with other data, they differentiate pathogenetic mechanisms in some patients and suggest therapeutic approaches in others.

Physiology and pathophysiology of the lower esophageal sphincter.

The physiologic factors controlling lower esophageal sphincter (LES) function are interrelated in a complex fashion and include the autonomic nerve supply, gastrointestinal hormones, and specific characteristics of the circular smooth muscle at the esophagogastric junction. It might be expected that a defect in any of these three controlling mechanisms would result in a clinically recognizable symptom complex. Abnormalities with either high or low LES pressure have been shown to relate to these specific aspects. Studies of the effects of various foods and other agents which decrease or increase LES pressure are of therapeutic interest in relating to patients with reflux symptoms. Decreases in LES pressure occurring after fat ingestion may explain a mechanism for many cases of fatty food intolerance. Pressure decreases after chocolate ingestion, after smoking, and after alcohol all have strong therapeutic implications in patients with chronic heartburn. Gastric alkalinization will increase pressure for up to one hour in patients with basal sphincter hypotension and reflux symptoms. Recent studies with drugs that work through the cholinergic mechanism have important therapeutic considerations. Anticholinergic agents produce definite decreases in LES pressure and are to provided in treatment of patients with reflux symptoms. On the other hand cholinergic drugs such as bethanechol have been shown to increase LES pressure in normal subjects and in patients with chronic sphincter incompetence. Recently, a double-blind therapeutic trial with bethanechol in patients with chronic heartburn has indicated that this drug, when given on regular basis, is an effective adjunct to therapy in these patients.