Diagnosis of asthma - a new approach.

Current definition of asthma involves four cornerstones: inflammation, hyperresponsiveness, bronchoconstriction, and symptoms. In research, the symptoms have had the slightest attention. According to international guidelines, the asthma symptoms are episodic breathlessness, wheeze, cough, tightness of the chest, and shortness of breath. As there are several symptoms, a primary question is how they are related to bronchoconstriction, the main clinical feature of asthma. Symptoms and lung function tests are regularly used for the evaluation of clinical health status and effect of treatment. However, there is no or poor correlation between these two variables, which means that they represent different mechanisms. Reduced lung function, such as a low FEV(1) , represents bronchial constriction, what do the symptoms represent? Some symptoms such as breathlessness and shortness of breath seem not to be evidence-based asthma symptoms. Focusing on bronchial obstruction is important in view of the potential risk of asthma attacks, but nonobstructive symptoms occur frequently and may also cause severe discomfort and poor quality of life. Interpreting all symptoms as signs of bronchoconstriction (asthma) may lead to misinterpretation when assessing health status and effect of treatment. Although a 'soft' variable, the strength of symptoms is that they are representing various mechanisms. The physiological preconditions for control and defense of respiration must be considered in the diagnostic process, regardless of inflammation, allergy, psychology, or other etiological factors. Based on studies on dyspnea in cardiopulmonary diseases, including asthma and asthma-like disorders, there seems to be a continuous spectrum of symptoms and mechanisms integrated in a single asthma syndrome.

Experience of an emergency mobile asthma treatment programme.

In order to reduce mortality and the need for hospital care for patients suffering from acute asthma, an emergency programme was set up. An ambulance crew, trained in coronary-pulmonary resuscitation was instructed in dealing with acute asthma and delegated to give 24 h treatment with bronchodilators (inhaled salbutamol and ipratropium bromide). If there was no, or only slight, improvement with this therapy, nurses (daytime) were delegated to give injections with corticosteroids (terbutaline and theophylline). Over a period of 2 years, 240 patients, 115 women and 125 men, were treated on 367 occasions. In 127 patients (53%), two or more treatments were given. The number of times treatment was given, as well as the proportion of females to males, increased the younger the patients were. Out of all the cases, more than 70% improved after treatment. On arrival, 21 patients (6%) were unconscious. After therapy, 15/21 patients (71%) survived. This may correspond to a similar reduction in mortality (population about 350,000 inhabitants), as it is unlikely that unconscious patients can survive without intensive care.

Prognosis among patients with out-of-hospital cardiac arrest judged as being caused by deterioration of obstructive pulmonary disease.

AIM: To describe the prognosis of patients with out-of-hospital cardiac arrest judged to be caused by the deterioration of obstructive pulmonary disease. PATIENTS: All patients in the community of Göteborg Sweden who suffered out-of-hospital cardiac arrest between 1980 and 1992 attended by our emergency medical service and in whom cardiopulmonary resuscitation was initiated. METHODS: The etiology of cardiac arrest was determined according to clinical history, observations at resuscitation and findings at autopsy. RESULTS: There were 3434 cardiac arrests of which 130 (4%) were judged to have been caused by deterioration of obstructive pulmonary disease. Of these patients 50% were found in asystole, 40% in pulseless electrical activity, and only 7% in ventricular fibrillation. Among patients with cardiac arrest caused by obstructive pulmonary disease 21 (16%) were hospitalized alive and six (5%) were discharged from hospital. Among patients who developed cardiac arrest after arrival of the ambulance, 16% were discharged from hospital versus 0% among patients who had arrest prior to arrival of the ambulance. CONCLUSION: Among patients with out-of-hospital cardiac arrest caused by deterioration of obstructive pulmonary disease, half were found in asystole. Overall, the survival rate was low. This highlights the importance of effective treatment early in the course of deterioration of obstructive pulmonary disease in order to avoid cardiac arrest.

Asthma and asthma-like disorders.

Bronchial asthma is defined as a chronic inflammatory disease resulting in a reversible and variable bronchial obstruction. For the clinical diagnosis of the disease there are some key indicators but as there is no 'gold standard' a correct diagnosis will sometimes not be obtained. Examples are patients in a symptom-free stage, current medication interfering with the methods used, patients with asthma-like symptoms reporting lack of effect of bronchodilators and patients who are unable to perform a forced expiration in an airway function test. The prevalence of asthma is reported to be 5-10%. The prevalence of asthma-like symptoms may be double this. The term 'asthma-like' has been used to an increasing extent during the last few years, which may indicate an increasing awareness of the fact that asthma-like symptoms are not always classical asthma. In this overview some disorders with asthma-like symptoms, especially in adults, are presented. The spectrum of differential diagnoses in a clinic may depend on which doctor/specialist the patient is consulting. In an asthma and allergy clinic it has been found that the most common differential diagnoses are chronic obstructive pulmonary disease (COPD), nonasthmatic cough and sensory hyper-reactivity (SHR), a disorder which is sometimes mixed up with asthma due to similar symptoms (heavy breathing, cough, increased secretion, difficulty in getting air etc.) and similar trigger factors (smoke, strong scents, exercise, cold air etc.). Recently it has been suggested that a capsaicin inhalation test may be an objective test for identifying patients with SHR. In asthma effective treatment is available today but in asthma-like disorders, such as SHR, no effective therapy is available, underlining the need of further research for understanding the pathophysiological mechanisms.

Asthma and asthma-like disorder, a 5-year follow-up study.

Consecutive adult patients (n = 70) referred for investigation of suspected asthma were reinvestigated after 5 years with the same diagnostic procedures (airway symptom score, spirometry, methacholine test) as used at the initial investigation. The same diagnostic criteria for asthma, asthma-like disorder (current asthma-like symptoms but negative asthmatests)and chronicobstructive pulmonary disease (COPD) were used at both visits. At the first visit 39/70 patients (56%) fulfilled the asthma criteria, 21/70 (27%) fulfilled the asthma-like criteria and 5/70 (7%) the COPD criteria. Due to lack of current symptoms 5/70 (7%) could not be classified. 5/70 patients (7%) were smokers, however, in the majority (72%) smoke was not tolerated as it induced asthma-like symptoms. At the investigation, 5 years later, 30/39 patients (76%) still fulfilled the asthma criteria and 12/21 patients (57%) still fulfilled the asthma-like criteria. At the 5-year investigation, 10% of patients in the asthma group now fulfilled the asthma-like criteria and 10% of patients in the asthma-like group fulfilled the asthma criteria. It is concluded that asthma as well an asthma-like syndrome may persist for 5 years or more. It is also concluded thatthe two disorders are closely related as patients in the asthma group over time could move into the diagnostic criteria ofthe asthma-like disorder and vice versa.

Exercise-induced respiratory symptoms are not always asthma.

Eighty-eight patients with a history of exercise-induced respiratory symptoms performed a maximal exercise test in order to study the reasons for stopping the test. There was a wide range of percentage maximal fall in peak expiratory flow (PEF), from minus 3% to 63%, mean 11%, recorded 0-30 min, mean 12 min after the break. In the controls the maximal decrease was 0-16%, mean 6%. Diagnostic criteria for asthma were fulfilled by 48 patients (55%). Of these patients 42% had a fall in PEF > or = 15% (exercise-induced asthma). Of the non-asthma patients 10% had a fall > or = 15%. The most common reason for stopping the exercise in the asthma group was breathing troubles (46%), the most common reason in the non-asthma group was chest pain/discomfort (35%). In about 20% of the patients dizziness and/or pricking sensations in arms or legs indicated hyperventilation as an additional reason for stopping the exercise. It is concluded that other kinds of reaction, than bronchial obstruction such as breathing troubles not directly related to bronchial obstruction and chest pain, may be important factors that can restrict physical capacity in patients with exercise-induced respiratory symptoms.

Capsaicin inhalation test for identification of sensory hyperreactivity.

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.

Differences in trigger factors and symptoms between patients with asthma-like symptoms and patients with asthma: development of a basis for a questionnaire.

Patients with asthma-like symptoms but with negative asthmatests are often misdiagnosed as having asthma and treated as asthmatics. They describe their trigger factors and symptoms very similar to those of patients with asthma. The aim of the study was to analyze differences in symptoms and trigger factors between asthma-like patients and asthmatics in order to elaborate a basis for a questionnaire for epidemiological and clinical use. A questionnaire with 54 questions about trigger factors and 137 questions about symptoms was sent to 40 patients with asthma-like symptoms and 40 with asthma, all consecutively selected from patients referred to an out-patient clinic for asthma and allergy for investigation of suspected asthma. Data were analyzed statistically in two steps using multiple logistic regression analysis. Significant differences were seen in several trigger factors and symptoms after the first analysis. After the second analysis, seven out of the 54 trigger factors and 22 out of the 137 symptoms emerged as those that most significantly discriminated between the two patient groups. These trigger factors and symptoms can be the basis of a new questionnaire with high discriminating power. Before using it, it is important to evaluate the best combination of variables, add some demographic variables and totestthe reliability and validity ofthis new questionnaire.

Mild experimental exacerbation of asthma induced by individualised low-dose repeated allergen exposure. A double-blind evaluation.

Low doses of environmental allergens have been proposed to increase bronchial hyperreactivity in sensitised individuals, without causing immediate asthmatic reactions. The primary aim of the present study was to evaluate whether repeated low doses of allergen, that do not cause overt bronchoconstriction, cause augmented non-specific bronchial reactivity. A secondary aim was to evaluate whether any changes in reactivity are associated with increased variability of lung function, and whether signs of inflammatory activity could be found. To do this, mild asthmatic patients without regular symptoms, but with both immediate and late reactions in response to a high dose of inhaled cat allergen extract, were included in a double blind, placebo controlled, cross-over study in which a low dose of allergen was administered on four consecutive days (Monday to Thursday). The dose of allergen was individualised for each patient, and was calculated to be 25% of the total dose given to produce an immediate and late response at screening. Repeated low dose allergen exposure produced a significant increase in methacholine reactivity compared to placebo, whereas FEV1 in the morning did not significantly change during the allergen week. Each low dose allergen exposure caused small changes in FEV1 (approximately 7% drop), which was significant vs. placebo only on day 2 (Tuesday). During the allergen week, six of eight patients reported asthma symptoms on at least one occasion, and variability in lung function, measured with a portable spirometer, was increased. Repeated low doses of allergen also produced a significant increase of P-ECP vs. placebo, without a significant rise in circulating eosinophils. However, no significant changes in circulating CD3, CD4, CD8, CD19, or CD25 cells were found, evaluated by FACS analysis. We conclude that low doses of allergen produce signs of a mild exacerbation of asthma, including increased bronchial reactivity to methacholine. This clinical model may be useful to evaluate both the pathophysiological mechanisms of asthma, and the effects of novel anti-asthma drugs.

Predictors of self-assessed work ability among subjects with recent-onset asthma.

The objective of the study was to find predictors for work disability among adults with recent-onset asthma. The study was performed in a group of 332 subjects with recent-onset asthma. The predictors were ascertained by structured interviews, pulmonary function measurements, methacholine challenge tests and skin prick tests. Asthma severity was classified into mild, moderate or severe, based on the minimum medication required to maintain asthma control. Work ability was based on self-assessment by inquiring about the subjects' present work ability, expressed in percent. The self-reported work ability decreased significantly with increasing number of days off work, indicating that self-reported work ability reflects the actual work ability. The majority (56%) of the subjects reported 100% working ability. Among women, but not among men, working ability was negatively correlated (rs = -0.33) with age. Among subjects with PC20 < 16 mg ml-1 work ability increased with increasing PC20. There was no relation between FEV1, FVC and working ability. Asthma severity and current respiratory symptoms at the work place showed a significant negative relation with work ability. In a logistic regression model, when controlling for age, gender, smoking and weekly working hours, decreased work ability was associated with asthma severity, respiratory symptoms at the workplace and PC20 < or = 4 mg ml-1. In conclusion, the work ability was assessed as normal in most asthmatic subjects. Significant predictors for decreased work ability were asthma severity, workplace-associated respiratory symptoms and bronchial hyperresponsiveness. The results indicate that work ability among asthmatics could be improved by reducing the workplace-associated symptoms, either by reducing the exposure to triggers or by improving the asthma therapy.

The inflammatory marker serum eosinophil cationic protein (ECP) compared with PEF as a tool to decide inhaled corticosteroid dose in asthmatic patients.

The objective of this study was to compare the inflammatory marker eosinophil cationic protein (ECP) with peak expiratory flow (PEF) in determining the therapeutic needs of inhaled corticosteroids in asthma patients assessed as asthma symptoms. A randomized, single-blind study over 6 months was performed at six specialist centres in Europe. In total, 164 adult patients with moderate to severe symptomatic asthma and regular use of inhaled corticosteroids were included. After a run-in period of 2 weeks patients were randomly allocated to the ECP or the PEF monitoring group. The dose of inhaled cort costeroids was adjusted every fourth week based on the current serum ECP value or pre-bronchodilator morning PEF values as surrogate markers of therapeutic needs. At the end of the study there were no statistically significant differences in the mean daily symptom score or the percentage of symptom-free days between the two groups. The mean daily dose of inhaled corticosteroids was similar in the two groups at the start of the study but the algorithms used to adjust the dose of inhaled corticosteroids resulted in an increased use of inhaled corticosteroids in both groups. The mean daily dose of inhaled corticosteroids over the whole study period was significantly lower in the ECP group compared withthe PEF group (1246 vs. 1667 microg, P = 0.026). In the ECP group, forced expiratory volume in I sec (FEV)% predicted was lower at the end ofthe study compared with the begining (92% vs. 87%, P = 0 .0009), although there was no significant difference between the two groups. None of the used algorithms for ECP and PEF led to improvement in symptom scores, in spite of increased doses of inhaled corticosteroids. In this respect, both methods were equivalent and insufficient. Recommendations suggesting lung function tests in current guidelines may be difficult to translate into clinical practice, however, a combination of inflammatory markers, lung function and symptoms may still improve asthma control.

Psychological differences between asthmatics and patients suffering from an asthma-like condition, functional breathing disorder: a comparison between the two groups concerning personality, psychosocial and somatic parameters.

Fifteen patients with asthma were compared with thirteen patients with asthma-like symptoms but without physiological signs of asthma. This condition is termed Functional Breathing Disorder, FBD. All patients were examined with regard to relevant physiological variables, and to specific personality traits and psychosocial status by means of psychological tests and questionnaires. The results indicated that the patients suffering from FBD were more psychologically distressed and had lower quality of life than the asthma patients. Further, they suffered from a significantly greater variety of symptoms and more intense symptoms than the asthmatics. Such symptoms included sleeping disturbances and somatic symptoms such as chest pain, cold hands or feet, blurred vision. The FBD patients had significantly more problems in their social and family lives, at work and in their leisure time than the asthmatics. They were significantly more depressed, less hedonic and more hypochondriac than the asthmatics. Moreover, they trusted other people to a significantly lesser degree. The patients with FBD had been hospitalized less often than the asthmatics, but they had sought medical care more often. The present study indicates that it is important to identify patients suffering from FBD at as early a stage as possible in order to offer them proper treatment.

[Histamine and methacholine tests in cases of sensitive bronchi--a 10-year experience]. / Histamin- och metakolintest av känsliga luftrör--tio års erfarenhet.

Ten years' experience of standardised bronchial histamine and methacholine tests is presented. For measuring non-specific hyperreactivity was used an internationally adopted dose-response technique, where histamine or methacholine is inhaled at doses increasing in two-fold steps. The fields of application have been clinical research on hyperreactivity, the diagnosis of asthma, evaluation of anti-asthmatic drugs, establishing (or excluding) the presence of bronchial obstruction or functional breathing disorder--the latter being a relatively new field. On the basis of this experience, the existence of a relationship between subjective hyperreactivity and breathing complaints has been hypothesized; and in clinical studies the place of histamine and methacholine tests as diagnostic aids in cases of bronchial asthma or functional breathing disorder has been better established. The tests yield information as to any tendency to develop bronchospasm, but must always be combined with other diagnostic tests and the taking of a careful history. Some important findings are reported--e.g., abnormal and steep dose-response curves, false low FEV1 values, or the occurrence of non-asthmatic symptoms during testing--which have not previously been fully considered in published reports, and which may lead to incorrect interpretation of test results.

[Severe asthma was found to be an asthma-like condition. Consider reduced doses of cortisone]. / Svor astma visade sig vara astmaliknande tillstånd. Beakta möjligheten sänka kortisondosen.

A middle-aged man with variable breathing problems and frequent acute attacks, diagnosed as severe bronchial asthma, was given high-dose oral corticosteroid treatment. Owing to the somewhat atypical history, and normal lung function test results despite severe concomitant asthma-like symptoms, the diagnosis was reconsidered. As a new diagnostic work-up showed the presence of a disease of slight to moderate severity, it was decided to taper off the corticosteroid treatment. Within one year the daily dose of prednisolone was decreased from 40 to 7.5 mg without deterioration of the airway symptoms or impairment of lung function. Re-evaluation also showed the principal diagnosis not to be bronchial asthma but an asthma-like condition (functional breathing disorder combined with sensory hyperresponsiveness), and alternative not previously considered and a condition in which steroids are without apparent effect. This case illustrates the importance of a critical re-view of the diagnosis before high-dose corticosteroid treatment with its inevitable side effects is instituted.

Physiotherapy in asthma using the new Lotorp method.

BACKGROUND: Physiotherapy in bronchial asthma has given various results. AIM: To test a new method focusing on breathing exercise and massage of the thoracic muscles. PATIENTS AND METHODS: Twenty-eight adult patients with a physician-diagnosed asthma were studied during 6 weeks. All patients were prescribed asthma medication. The new method [active group, n = 17) was compared with physical training (control group, n = 12). RESULTS: PEF was significantly improved (p = 0.001) in the active group, however, FEV1 showed no significant change. The symptoms "tightness of the chest", "difficult breathing in", "air hunger", and the individually dominating symptom (p = 0.001) were significantly reduced in the active group. Exercise-induced breathing troubles and chest expansion were also significantly reduced. CONCLUSION: Physiotherapy including breathing exercise and massage of the thoracic muscles (the Lotorp method) in patients with physician-diagnosed asthma resulted in significantly reduced respiratory symptoms during rest and exercise and increased chest expansion. The improvements may be due to an increased mobility of the chest and diaphragm.

Early and late phase asthmatic response in lower airways of cat-allergic asthmatic patients--a comparison between experimental and environmental allergen challenge.

BACKGROUND: Standardized experimental allergen challenges are usually adopted to investigate the effect of allergen exposure on the lower airways. Environmental (natural) allergen challenges are used less often, mainly because of difficulties in standardizing the method, safety reasons and costs. The aim of this study was to investigate the relationship between an experimental and an environmental bronchial challenge. For this reason a natural challenge model was developed. METHODS: Sixty-two patients with a history of cat allergen-induced symptoms involving the lower airways, positive skin prick test, positive in vitro specific IgE to cat allergen and bronchial hyper-responsiveness were included. All 62 patients underwent an experimental challenge in the laboratory followed by an environmental allergen challenge. RESULTS: All 62 patients developed an early asthmatic response [>or=20% fall in forced expiratory volume in 1 s (FEV1)] in the experimental challenge and 60% (37/62) during the environmental challenge. A late asthmatic response (>or=15% fall in FEV1 within 3-24 h) was seen in 56% (35/62) of the patients after the experimental challenge. Following the environmental challenge 47% (29/62) of the patients developed a late response. Thirty-four per cent (21/62) of the patients developed a late response in both challenge models and 31% (19/62) did not develop a late response in any model. Thus, there was consistency in 65% (40/62) of the patients in both challenge models. CONCLUSION: We found consistency in the pattern of response to inhaled allergen between the two challenge models and we believe that experimental bronchial challenge is likely to reflect the development of relevant inflammation in the lower airways after low-dose allergen exposure in the environment.

Therapeutic modulation of bronchial hyperreactivity.

At the department of allergology is Göteborg clinical models have been developed for studies of the allergen-induced and histamine- (and metacholine-) induced bronchial hyperreactivity. The reproductability in carefully selected asthmatic patients has been found to be acceptable. One of the aims has been to evaluate the clinical effect of new anti-allergic drugs. The importance for clinical methods has increased as experimental studies in animals have been found to be of limited predicted value. In drugs such as KWD 2131 and ketotifen more than one fundamental mechanism of action has been found. In those drugs we have tried to separate the different anti-asthmatic effects by using bronchial histamine provocations in combination with allergen provocations. The presentation will include a discussion of the provocation models used and the results of clinical trials on anti-allergic drugs.

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.

Bronchial hyperreactivity after treatment with sodium cromoglycate in atopic asthmatic patients not exposed to relevant allergens.

The bronchial hyperreactivity, measured as the responsiveness to histamine, was studied in 14 atopic patients before, during, and after 4 wk of treatment with sodium cromoglycate (SCG) and placebo in a double-blind, randomized, crossover study. The patients were not exposed to relevant allergens during the study. The variations in provocation concentrations corresponding to 20% decrease in FEV1 (PC20) were small during both placebo and active drug treatment. After SCG treatment, PC20 increased (less responsiveness) in nine of the 14 patients, especially in those with low PC20 values. The difference between placebo and active drug treatment was not statistically significant. Although SCG has a mediator-inhibiting effect, this study gave no support for the assumption that inhibition of mediator release leads to a reduction of the bronchial hyperreactivity in atopic asthmatic subjects who are not exposed to relevant allergens.