Physical capacity and dyspnea in patients with asthma-like symptoms but negative asthma tests

Ringsberg KC, Wetterqvist H, Löwhagen O, Sivik T. Physical capacity and dyspnea in patients with asthma-like symptoms but negative asthma tests.
Ten female patients with asthma-like symptoms but negative asthma tests 'study group' were compared with 10 female asthmatics in an exercise test with and without pretreatment with β₂-stimulants. The aim was to determine whether the asthma-like symptoms in the patients of the study group could be explained by bronchoconstriction, circulatory abnormalities, or physical unfitness when provoked physically, and whether the exercise test could be used to distinguish these patients from asthmatics. Without pretreatment, the asthma group reacted with bronchoconstriction, as indicated by postexercise systematic changes in PEFR, FEV₁, FVC, and S a_o2, which were not seen in the study group. The groups differed in the ratings of "difficulty in getting air", as only the asthma group had significantly lower ratings when pretreated. The study group's mean test performance was 94 W; the asthma group's was 106 W. The low performance was not explained by disturbances in heart rate, electrocardiogram, or blood pressure or physical unfitness. The exercise test was found to distinguish between the groups, especially for bronchoconstriction, oxygen saturation, and ratings of dyspnea. It could be used complementary to lung function tests to eliminate bronchoconstriction, circulatory abnormalities, and physical unfitness as a cause of the asthma-like symptoms.     

Clinical health education for patients with asthma-like symptoms but negative asthma tests

BACKGROUND: Patients with asthma-like symptoms but negative asthma tests often state that they lack strategies to cope with their symptoms. The aim of the study was to determine whether a problem-based health education program had a beneficial effect on the participants' experience of symptoms and subjective health. METHODS: Thirty-eight patients, consecutively drawn from an outpatient clinic for asthma and allergy, were randomly allocated to an intervention group (I group, n=18) and a control group (C group, n=20). The I group, divided into three subgroups, met on seven occasions over 5 months. The program had a multidisciplinary approach, used exercises inspired by cognitive behavioral therapy, and was performed according to the principles of problem-based learning. All patients answered the Nijmegen Symptom Questionnaire (NQ) and the SF-36 health survey before and 2 months after the training was terminated. RESULTS: Before the program, there were no significant differences between the groups in their earlier experience of symptoms. After it, the I group scored significantly lower on shortness of breath (P=0.001) and central tetany (P=0.05) than the C group. On both test occasions, the asthma-like patients scored lower on all variables of the SF-36 than the reference groups of asthmatics and healthy subjects. No significant differences were seen between the I group and the C group except for vitality, in which the C group scored lower before the intervention. CONCLUSIONS: Patients with asthma-like symptoms but negative asthma tests benefit from taking part in a problem-based health education program. It mainly reduces the frequency of symptoms.     

Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms

BACKGROUND: A group of patients with asthma-like symptoms and sensitivity to chemical irritants, but without bronchial obstruction, has been found among subjects referred for suspected asthma. They have no well-defined diagnosis, and no objective diagnostic method has previously been available. These patients are more sensitive to inhaled capsaicin than are patients with asthma or healthy controls. The aim was to study cough and other capsaicin-induced symptoms and to test the effect of a drug (lidocaine) that inhibits nerve transmission in sensory nerves. METHODS: Twelve patients were provoked with three different concentrations of inhaled capsaicin solutions in a randomized, double-blind order. They all had asthma-like symptoms and were sensitive to chemical irritants, but had no IgE-mediated allergy or demonstrable bronchial obstruction. Before the provocations, the patients inhaled lidocaine or placebo (saline), also in a double-blind, randomized order. The results were expressed as the number of coughs and scores of various symptoms. RESULTS: The patients reacted in a dose-dependent way with cough, airway, and eye symptoms, which were significantly reduced after preinhalation of lidocaine. CONCLUSIONS: A drug that inhibits transmission in sensory nerves successfully blocked the number of coughs and other symptoms provoked by inhalation of capsaicin. This indicates that the mechanisms underlying chemical sensitivity in these patients may originate in the sensory nervous system, and we call this condition "sensory hyperreactivity".     

Placebo-controlled challenges with perfume in patients with asthma-like symptoms

A group of nine patients with respiratory symptoms after nonspecific irritating stimuli, but without any IgE-mediated allergy or demonstrable bronchial obstruction, were referred to the asthma/allergy outpatient department for evaluation of suspected asthma. In order to find a provocation model and objectively assess these patients' symptoms in controlled studies, provocation with perfume or placebo was performed. The same patients were also subjected to perfume provocation with or without a carbon filter mask to ascertain whether breathing through a filter with active carbon could prevent the symptoms. The patients breathed through the mouth during the provocations, as they used a nasal clamp to prevent any smell of perfume. We found that the patients' earlier symptoms could be verified by perfume provocation. Breathing through the carbon filter had no protective effect. The conclusion is that symptoms suggesting hyperreactivity of the respiratory tract and asthma can be provoked by perfume without the presence of bronchial obstruction, and that using a carbon filter mask has no preventive effect. The symptoms are not transmitted via the olfactory nerve, since the patients could not smell the perfume, but they may have been induced by a trigeminal reflex via the respiratory tract or by the eyes.     

Psychological triggers and hyperventilation symptoms in asthma.

BACKGROUND: Anecdotal accounts have identified hyperventilation as one route through which psychological factors can trigger bronchoconstriction. However, little is known about the empirical association between psychological and other trigger factors and hyperventilation in asthma exacerbations. OBJECTIVE: To study the cross-sectional association between perceived triggers and hyperventilation symptoms in 1 British and 1 German sample of patients with asthma who were recruited from the community and from primary care clinics. METHOD: Patients completed relevant language versions of the Asthma Trigger Inventory and the Asthma Symptom Checklist. RESULTS: After controlling for demographics and asthma severity, perceived asthma triggers measured by subscales of the Asthma Trigger Inventory explained 12.5% to 37.3% of the variance in Asthma Symptom Checklist hyperventilation-hypocapnia symptoms. Psychological triggers accounted for 10.6% to 26.7% of the variance alone and 4.3% to 11.0% of the variance over and above other trigger factors. In contrast, perceived animal and pollen allergen triggers did not contribute unique variance to the hyperventilation symptom report. Psychological triggers did not explain variance in classic airway obstruction symptoms, thus arguing against a general bias toward inflated symptom reports in patients with psychologically induced asthma. CONCLUSION: Differences in perceived asthma triggers are substantially associated with hyperventilation symptoms, and patients with more frequent psychological triggers also tend to report that they experience more hyperventilation symptoms during their asthma symptom episodes.     

Effects of high and low anxiety provoking instructions on the responses to the hyperventilation provocation test

This study examined the effect of high and low anxiety provoking instructions in subjects submitted to a Hyperventilation Provocation Test (HVPT). Subjects were 43 out-patients referred to our clinic for a diagnostic examination of Hyperventilation Syndrome (HVS). Results showed that anxiety levels were affected by the instruction manipulation, but the magnitude of this effect was less than expected and the instruction manipulation had no effect on intensity arid type of reproduced symptoms, nor on symptom recognition. Subjects who met Diagnostic and Statistical manual of Mental Disorders (3rd ed., rev,; American Psychiatric Association, 1987) criteria for Panic Disorder (PD) were not more responsive to the instruction manipulation than non-PD patients. It is argued that the small effect of the manipulation is probably not due to the solidity of the HVPT but to the pervasiveness of pretest cognitions and expectations. In line with this, the report of HVS symptoms appeared highly related to psychological trait measures like anxiety, fear of bodily sensations, and a general tendency to report somatic symptoms.     

Systematic review: Exposure to pets and risk of asthma and asthma-like symptoms

BACKGROUND: Studies of exposure to pets and risk of asthma have yielded conflicting results. OBJECTIVES: We performed a systematic review to synthesize the evidence of the effect of exposure to pets in the home on the risk of asthma and asthma-related symptoms. We also assessed differences between the studies as sources of heterogeneity of the results. METHODS: We conducted a MEDLINE search (until the end of 1999) using the following boolean search command: (asthma[all] OR wheez*[all]) AND (domestic animal*[all] OR pets[all]). The outcome was limited to either diagnosis of asthma or the symptom of wheezing. The exposure of interest was domestic animals in the home. Appropriate temporal relationship was defined as present in studies with either pet keeping within the first 2 years of life, in the past, or exposure to pets preceding the outcome. RESULTS: Thirty-two of the 217 retrieved articles fulfilled the eligibility criteria. Inappropriate time sequence of the exposure and outcome information was an important source of heterogeneity and an indication of potential selection bias. Therefore we analyzed studies focusing on early exposure or ensuring appropriate temporal sequence. The pooled risk estimates for both asthma (fixed-effects odds ratio, 1.11; 95% CI, 0.98-1.25; heterogeneity, P =.04; random-effects odds ratio, 1.09; 95% CI, 0.89-1.34) and wheezing (fixed-effects odds ratio, 1.19; 95% CI, 1.05-1.35; heterogeneity, P =.03; random-effects odds ratio, 1.17; 95% CI, 0.95-1.44) indicated a small effect, which was limited to studies with a median study population age of over 6 years (fixed-effects odds ratio, 1.19; 95% CI, 1.02-1.40; heterogeneity, P =.04; random-effects odds ratio, 1.15; 95% CI, 0.86-1.56; fixed-effects odds ratio, 1.29; 95% CI, 1.12-1.48; heterogeneity, P =.31). In younger children the harmful effect disappeared for wheezing (odds ratio, 0.80; 95% CI, 0.59-1.08; P =.38). CONCLUSION: Exposure to pets appears to increase the risk of asthma and wheezing in older children. The observed lower risk among exposed than among unexposed young children is consistent with a protective effect in this age group but could also be explained by selection bias.     

Alexithymia,empathy, negative affect and physical symptoms in patients with asthma

Although alexithymia has been found to be associated with physical symptoms in psychosomatic disorders such as asthma, mechanisms linking this association are unknown. However, affective alexithymic features may be associated with physical symptoms in the presence of deficits in affective characteristics such as low empathy and high negative affect. This study aimed to assess direct effects of alexithymic traits on physical symptoms and indirect effects of these subscales through empathy and negative affect (e.g. depressive, anxious and stress symptoms) by controlling for asthma severity in patients with asthma. Three hundred patients with asthma completed the Toronto Alexithymia Scale‐20 (TAS‐20), the Basic Empathy Scale (BES), the Depression Anxiety Stress Scales‐21 (DASS‐21) and the Physical Symptoms Inventory (PSI). After controlling for asthma severity, the results showed that alexithymia subscales of the TAS‐20 had no direct effects on physical symptoms, but the difficulty in identifying feelings (DIF) subscale of the TAS‐20 was associated with affective empathy and negative affect. Affective empathy was significantly related to negative affect. Affective empathy and negative affect were associated with physical symptoms. The affective subscale of alexithymia on the TAS‐20, that is DIF, indirectly affected physical symptoms through affective empathy and negative affect. Findings suggest that patients with asthma who have high levels of DIF may show high physical symptoms in the presence of low affective empathy and high negative affect.     

Vasospastic ischaemia induced by the hyperventilation test in patients with a negative response to ergometrine

We present the case histories of two patients with angina pectoris who developed coronary artery spasm in response to provocation with prolonged hyperventilation (verified by ST segment elevation in both and coronary angiography in one) despite a negative ECG response to intravenous injection of 0.4 mg ergometrine. This new observation, which is in conflict with recent publications stating that ergot provocation is more sensitive than hyperventilation, suggests that in some patients diagnostic provocation with hyperventilation may be an alternative to the widely used ergot provocation.     

Papain-induced asthma: diagnosis by skin test, RAST and bronchial provocation test

Seven out of eleven workers occupationally exposed to airborne papain developed immediate hypersensitive reactions, predominantly asthma and rhinitis. Skin tests and RAST with papain were positive in all symptomatic workers, but not in the four asymptomatic workers. Furthermore, out of forty non-exposed asthmatics, thirty-eight had negative RAST results and all had negative skin test results. Bronchial provocation tests with 0.15–0.5 mg papain performed in five patients with a positive case history showed in each case an immediate asthmatic reaction; in addition to that, one patient developed signs of a dual asthmatic reaction. Our results suggest that airborne papain is a highly immunogenic agent in humans, which induces type I allergic reactions in a large percentage of the exposed subjects.     

Effects of voluntary hyperventilation on cortical sensory responses Electroencephalographic and magnetoencephalographic studies

 It is well established that voluntary hyperventilation (HV) slows down electroencephalographic (EEG) rhythms. Little information is available, however, on the effects of HV on cortical responses elicited by sensory stimulation. In the present study, we recorded auditory evoked potentials (AEPs) and magnetic fields (AEFs), and somatosensory evoked magnetic fields (SEFs) from healthy subjects before, during, and after a 3- to 5-min period of voluntary HV. The effectiveness of HV was verified by measuring the end-tidal CO₂ levels. Long-latency (100–200 ms) AEPs and long-latency AEFs originating at the supratemporal auditory cortex, as well as long-latency SEFs from the primary somatosensory cortex (SI) and from the opercular somatosensory cortex (OC), were all reduced during HV. The short-latency SEFs from SI were clearly less modified, there being, however, a slight reduction of the earliest cortical excitatory response, the N20m deflection. A middle-latency SEF deflection from SI at about 60 ms (P60 m) was slightly increased. For AEFs and SEFs, the center-of-gravity locations of the activated neuronal populations were not changed during HV. All amplitude changes returned to baseline levels within 10 min after the end of HV. The AEPs were not altered when the subjects breathed 5% CO₂ in air in a hyperventilation-like manner, which prevented the development of hypocapnia. We conclude that moderate HV suppresses long-latency evoked responses from the primary projection cortices, while the early responses are less reduced. The reduction of long-latency responses is probably mediated by hypocapnia rather than by other nonspecific effects of HV. It is suggested that increased neuronal excitability caused by HV-induced hypocapnia leads to spontaneous and/or asynchronous firing of cortical neurones, which in turn reduces stimulus-locked synaptic events. Received: 14 October 1997 / Accepted: 28 October 1998     

Diagnostic value of the nasal provocation test with Dermatophagoides pteronyssinus in childhood asthma

We aimed to determine whether the nasal provocation test (NPT) with allergen could be used as a diagnostic test in asthmatic children with or without allergic rhinitis, and whether it had any effects on pulmonary function tests and arterial oxygen saturation (SaO₂) values. Therefore, 25 asthmatic outpatients sensitive to Dermatophagoides pteronyssinus (Dp), aged 6–17 years, 12 having allergic rhinitis, and 10 nonatopic children as a control group were challenged intranasally with solution containing Dp extract by administration of a total dose of 800–1000 AU to both nasal cavities. Before the test and 10 min and 20 min after the administration of the allergen intranasally, the nasal expiratory peak flow (NEPF), pulmonary function tests, and SaO₂ were measured. In the NPT, a decrease of 20% or more in NEPF and occurrence of nasal symptoms were considered to be positive. NPT was positive in all the asthmatic patients with or without allergic rhinitis, while all the children in the control group had a negative test. Compared to values prior to the test, values of FEV₁, (forced expiratory volume in 1 s) and SaO₂ showed no statistically significant decrease, and no clinically significant asthmatic reaction was observed in any of the groups. Our study suggests that in asthmatic children with or without allergic rhinitis, the NPT with allergen is a simple, safe, and useful diagnostic test.     

Prevalence of asthma and asthma-like symptoms in young adults living in three east Anglian towns.

BACKGROUND. The European Community respiratory health survey is examining the prevalence of asthma and risk factors for asthma. AIM. As part of this multinational survey, a study was undertaken to determine the prevalence of asthma and asthma-like symptoms in young adults living in Cambridge, Ipswich and Norwich using a postal questionnaire. METHOD. A previously validated symptom questionnaire was sent to 2500 men and 2500 women aged 20-44 years living in and registered with a general practitioner in each of the three towns. RESULTS. In total, approximately 9000 adults responded. The prevalence of symptoms suggestive of asthma was found to be similar in the three towns. Of respondents, 8% reported having been woken by an attack of shortness of breath at some time in the last 12 months, higher than previously reported. Five per cent reported having had an asthma attack. CONCLUSION. General practitioners wishing to examine asthma prevalence in their own practice population could use a similar methodology.     

Hypertonic saline cough provocation test with salbutamol pre-treatment: evidence for sensorineural dysfunction in asthma

Background Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. Objective To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. Methods Nineteen healthy subjects, 21 non‐asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre‐treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. Results The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). Conclusion The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough‐provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.     

Nasal provocation test with lysine acetylsalicylate in aspirin-sensitive patients

The authors have studied nasal provocation testing (NPT) with aspirin in 45 aspirin-sensitive patients (40 affected by nasal polyposis) and in 38 aspirin-tolerant patients (27 affected by nasal polyposis). The test was positive in 37.7% of aspirin-intolerant subjects, but only in 7.9% of subjects in the control group (P less than .01).     

Clinical and bronchial provocation studies in patients with meatwrappers' asthma

Reactive airway disease has been observed in meatwrappers employing polyvinyl chloride (PVC) soft wrap film and thermally activated price labels. Sixty-nine percent of 96 meatwrappers responding to a mail survey had work-related respiratory, mucous membrane, or systemic complaints. Smokers developed more pronounced symptoms than nonsmokers. Work-simulated bronchial provocation tests were carried out in 14 symptomatic meatwrappers. Following a 3-hr exposure to polyvinyl chloride fumes, 3 of 11 workers developed a mean decrease of 25% in FEV₁ and 7 of 11 workers developed a mean decrease of 13 mm Hg in their PaO₂. Following a 30-sec to 20-min exposure to price label adhesive fumes, 9 of 13 workers developed a mean decrease of 49% in FEV₁ and 12 of 13 developed a mean decrease of 20 mm Hg in their PaO₂. Though a hypersensitivity reaction to one or more components in PVC or price label adhesive emissions is suspected, the precise pathogenesis of this syndrome remains unknown. The entire spectrum of meatwrappers' syndrome must be interpreted as a complex response to both PVC and price label adhesive fume exposure.     

Differential cell count of sputum in patients with asthma challenged with allergen provocation

Inhalation of hypertonic saline aerosol is a noninvasive method of obtaining sputum for examination of inflammatory processes in the airways. The aim of our investigation was to evaluate the effect of the bronchial provocation test with Dermatophagoides pteronyssinus on both total and differential cell counts in the sputum of allergic asthma patients. The studies were carried out on 20 mild or moderate allergic asthmatics. In each case the studies were performed on three consecutive days. Sputum was induced on the first day of the study, the next day the bronchial provocation test with the allergen was performed and on the last day the sputum induction was repeated again. Twenty-four hours after the allergen challenge an increase in the total cell count and in eosinophils and a decrease in the percentage of macrophages were found in the induced sputum. The above changes were more marked in the patients demonstrating the dual asthmatic reaction after allergen challenge.     

Prevalence of asthma,asthma-like and allergic symptoms in the urban and rural adult population in Eastern Turkey

There is no study assessing the prevalence rates for asthma, asthma-like symptoms, and allergic symptoms in Eastern Turkey. In this study, we investigated these rates in the urban and rural adult population of Elazig Region in Eastern Turkey. A questionnaire was prepared based on the standard inquiry form of the European Community Respiratory Health Survey. The survey included 3,591 consented adults who were randomly selected. Each questionnaire was interviewed face-to-face by a physician. It was found that the cumulative prevalence rates of asthma and asthma-like symptoms of the rural and the urban respondent groups were 29.6% and 25.8%, respectively. The periodic prevalence rates of the same symptoms were 27.3% and 19.3%, respectively. The percentages of the patients living in rural and urban areas diagnosed as asthma by a physician were 5.5% and 3.1%, respectively. The proportions of patients with a history of at least one allergic disorder were 36.4% and 23.7% in the rural and urban groups, respectively. Asthma and asthma-like symptoms in patients with allergic rhinoconjunctivitis were significantly higher than those without (p < 0.01). The cumulative rates of a previous diagnosis of asthma among respondents with a history of asthma-like symptoms were 18.4% in the rural and 11.2% in the urban groups (p < 0.05). Among those who had had periodic asthma-like symptoms, the rural and urban rates of previous asthma diagnosis were 18.6% and 14.3%, respectively (p < 0.01). Unexpectedly, the prevalence rates for asthma, asthma-like and allergic symptoms in adults living in the rural areas of Elazig Region in Eastern Turkey were significantly higher than the rates in the urban population.