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[Proposal of a new classification of adult bronchial asthma--child onset asthma, adult onset asthma and adult relapse asthma. Project Team for Research into Adult Bronchial Asthma in Japan].

The first nationwide research into adult bronchial asthma in Japan proposed a new classification of adult asthma. Adult asthma was categorized into child onset asthma, adult onset asthma and adult relapse asthma. The frequency of child onset asthma, adult onset asthma and adult relapse asthma in adult asthma was 11.2%, 77.3% and 3.7%, respectively. The frequency of child onset asthma decreased markedly in the older age group. On the other hand, the frequency of adult onset asthma increased, and reached more than 90%, in the older age group. The frequency of the following factors: atopic asthma, complications with other atopic diseases, mild asthma, male patients, experience of mechanical ventilation, visits to night clinics and oxygen therapy on acute attack, was significantly higher in the child onset asthma group than in the adult onset asthma group. The frequency of infectious type, aspirin intolerance, steroid dependent asthma, severe asthma and regular medication was significantly higher in the adult onset asthma group. Adult relapse asthma seemed to fall between these two groups. Based on the above observations, we proposed a new classification of adult asthma which includes child onset asthma, adult onset asthma and adult relapse asthma.

Asthma

Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma.

We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined. Studies were assessed in 10 subjects with mild asthma, six methacholine-sensitive subjects without asthma, and 10 normal subjects. The density and affinity of beta-receptors and alpha-receptors were determined by Scatchard analysis. Our findings were that (1) subjects with asthma had a significantly lower density of beta-receptors compared to normal subjects, (2) subjects with asthma had a significantly lower cAMP response to isoproterenol stimulation compared to the two other groups, (3) in subjects without asthma. PAF decreased the basal cAMP level and significantly inhibited the response to isoproterenol stimulation, (4) there was no difference in density and affinity of platelet alpha-receptors or in platelet cAMP responses to stimulation by alpha-agonists among these three groups, and (5) neither cAMP response or beta-receptor density on mononuclear cells were significantly correlated with pulmonary-function tests (FEV/FVC times 100), sensitivity to methacholine, or cold-air inhalation. These results suggest that patients with asthma may have a lower isoproterenol cAMP response and decreased density of beta-adrenergic receptors on mononuclear cells in the absence of beta-agonist therapy. It is speculated that release of PAF and other mediators secondary to allergen exposure, even in the absence of overt attacks of asthma, may inhibit the response to endogenous or exogenous beta-adrenergic agonists.

Adolescent

Asthma Exacerbation Risk and School Asthma Readiness.

OBJECTIVES: School-based asthma management is a key facet of child asthma care. We aimed to describe the proportion of students whose schools have child-specific components of asthma care, derive a composite metric of these components ("school asthma readiness"), and assess its association with asthma exacerbations (asthma risk) in the preceding year. METHODS: Within a nested cohort of children enrolled in a larger randomized clinical trial, we assessed the baseline proportion of children whose school had elements of necessary asthma care. We then derived a "school asthma readiness" composite and used ordinal logistic regression to model the association between number of asthma exacerbations in the preceding year and the composite, accounting for demographic, clinical, and school characteristics. RESULTS: Of 202 participants aged 5 to 13 years, most identified as Black (95%) and non-Hispanic (98%), and most participants (73%) had an emergency department visit for asthma in the year before enrollment. Most students' schools (79%) had awareness of the child's asthma diagnosis, whereas fewer had reliever medications and valved holding chambers (both 31%) and asthma care plans (7%). Asthma exacerbations in the prior year were associated with a significantly higher school asthma readiness in bivariate (odds ratio [OR], 1.44 [95% CI, 1.14-1.82]; P = .002) and multivariable analysis (OR, 1.31 [95% CI, 1.02-1.7]; P = .037). CONCLUSIONS: A minority of children attended schools that were equipped to manage asthma symptoms. More past exacerbations were associated with higher school readiness, suggesting that more work is needed to support proactive asthma care in schools.

Humans

Facilitated referral to asthma specialist reduces relapses in asthma emergency room visits.

Facilitated asthma-specialist care delivered by allergists was compared to generalist care on the rate of relapse of asthma emergency room (ER) visits and hospitalizations and on asthma control in a prospective, controlled study of San Diego Kaiser Health Plan members with asthma. Subjects with asthma between the ages of 6 and 59 years presenting for acute ER care for asthma were systematically assigned by alternating, consecutively, the day of their ER visit to receive either (1) facilitated referral to an asthma specialist within the allergy department and concomitant comprehensive ongoing asthma care (intervention group, n = 149) or (2) continued outpatient management from generalist physicians (control group, n = 160). The course of their asthma was evaluated blindly during the subsequent 6 months by review of medical records, initial and follow-up questionnaires, and spirometry. Compared to the control group, the intervention group noted (1) a 75% reduction in the number of, and percent of, subjects with asthma awakenings per night (p less than or equal to 0.0001), (2) an almost 50% reduction in asthma ER relapses (p = 0.017) resulting from a reduction in the frequency of multiple relapse (p = 0.005), and (3) a greater use of inhaled corticosteroids (p less than 0.00001) and cromolyn (p = 0.002). Thus, facilitated referral of subjects with asthma to specialists in asthma therapy after acute ER therapy appears to reduce asthma ER relapses and to improve asthma outcome.

Adult

Cumulative Genetic Risk for Asthma Contributes to Disease Severity in Children with Asthma living in Urban Environments.

BACKGROUND: Childhood-onset asthma is highly heritable, with nearly 200 risk loci identified in genome-wide association studies. Aggregated polygenic risk scores can be used to quantify genetic predisposition to asthma, but their power to predict asthma severity in multi-ancestral groups has not been determined. OBJECTIVE: Our aim was to examine the predictive power of biobank-derived asthma polygenic risk scores in children with asthma living in urban environments. METHODS: We generated polygenic risk scores for asthma, derived from a large-scale genome-wide association meta-analysis, in four multi-ancestry asthma study cohorts of children living in urban environments. We assessed genetic predictions across different subphenotypes of asthma and tested for associations between genetic asthma risk and measures of asthma severity. RESULTS: Genetic asthma prediction was significantly stronger for more symptomatic asthma phenotypes (P<0.001). Polygenic risk scores were significantly higher in difficult-to-control vs. easy-to-control asthma (P=0.02). Genetic risk was also significantly associated with more frequent exacerbations (P=0.03), higher blood eosinophil levels (P=0.01), and lower lung function (P<0.001). CONCLUSION: Cumulative genetic risk for asthma is associated with disease severity and exacerbation risk in children with asthma living in urban environments.

Journal Article

The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms.

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.

Asthma

Asthma classification by pathophysiology and IgE-mediated allergic reaction: new concepts for classification of asthma.

Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE-mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome).

Adolescent

Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma.

A case-control study has previously been reported of asthma deaths in people aged 5-45 years who had a hospital admission for asthma (the index admission) in New Zealand during 1981-1987. The study has been re-analysed to examine the association between markers of asthma severity and risk of asthma death or hospital admission; patients prescribed fenoterol were excluded from this re-analysis because of the previously reported interaction between fenoterol, asthma severity, and asthma deaths. The re-analysis included 39 patients who died of asthma during the 12 months after their index admission, 226 patients who had a readmission for asthma during the 12 months after their index admission, and 263 controls chosen from all index admissions. An admission in the previous 12 months was the strongest marker of subsequent risk of death (odds ratio (OR) = 3.5, 95% confidence interval (CI): 1.8-6.9, P less than 0.01), and was also a strong marker of subsequent risk of readmission (OR = 3.0, 95% CI: 2.1-4.2, P less than 0.01); the risk increased with the number of previous admissions. Three or more categories of prescribed asthma drugs was also associated with subsequent death (OR = 1.7, 95% CI: 0.9-3.3, P = 0.13) or readmission (OR = 1.9, 95% CI: 1.3-2.7, P less than 0.01); prescribed oral corticosteroids was only weakly associated with subsequent death (OR = 1.3, 95% CI: 0.6-2.8, P = 0.59), but was more strongly associated with subsequent readmission (OR = 1.9, 95% CI: 1.2-2.8, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Morbidity associated with asthma and audit of asthma treatment in out-patient clinics.

A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma.

Adolescent

Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness.

Bronchial biopsy specimens were obtained by fiberoptic bronchoscopy from 21 atopic subjects with asthma, 10 atopic subjects without asthma, and 12 normal healthy control subjects. With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and counted in the bronchial mucosa. The mean number of leukocytes (CD45+) and T-lymphocytes (CD3+, CD4+, and CD8+) at two airway levels in the subjects with asthma tended to be higher than in the other groups, but this difference did not achieve statistical significance. Similarly, there were no significant differences in the numbers of mucosal-type or connective tissue-type mast cells, elastase-positive neutrophils, or Leu-M3+ cells in the airway mucosa of subjects with asthma compared with atopic subjects without asthma and healthy control subjects. In contrast, significantly more interleukin-2 receptor-positive (CD25+) cells and "activated" (EG2+) eosinophils (EOSs) were present in the airways of subjects with asthma at both proximal and subsegmental biopsy sites. When the relationships between numbers of T-lymphocytes, activated (CD25+) cells, and EOSs were analyzed, there were positive correlations between CD3 and EG2, between CD3 and CD25, and between CD25 and EG2 positive cells in the airways of subjects with asthma. Furthermore, the ratio of EG2+ to CD45+ cells correlated with the provocative concentration of methacholine that caused a 20% decrease of FEV1 in hyperresponsive subjects. Although these associations do not prove a causal relationship, the results support the hypothesis that activated (CD25) T-lymphocytes release products which regulate recruitment of EOSs into the airway wall. In addition, our findings suggest that, in the large airways at least, asthma is not associated with hyperplasia of either mucosal-type or connective tissue-type mast cell.

Adult

Later development of asthma in patients with a negative methacholine inhalation challenge examined for suspected asthma.

A negative methacholine inhalation challenge (MIC) in a patient with suspected bronchial asthma is generally considered to make this diagnosis unlikely. Nevertheless, the patient may later develop asthma. To estimate the proportion that eventually becomes asthmatic, a 10 year follow-up study was carried out on 334 consecutive MIC-negative patients aged 14-80 years. The development of asthma among these patients was assessed on the basis of entitlement to preferential refund from the cost of antiasthmatic therapy granted for them under national health insurance. During the follow-up 30 patients (9%) were granted the refund. There was no significant difference between men and women in this respect. Patients who developed asthma were somewhat older than those who did not. A family history of allergy, allergic rhinitis, and positive reactions to skin prick tests were significantly more common in patients with future asthma. These patients also had a lower mean forced expiratory volume in 1 sec (FEV1) (% of predicted) and a higher mean increase in PEF after an inhaled sympathomimetic than those remaining free from asthma. In multivariate analyses with a logistic model, 3 risk indicators proved independent predictors of future asthma: age, positive family history of allergy, and FEV1 (% of predicted).

Adolescent

Assessing the functional status during an asthma attack with Dartmouth COOP charts. Validity with respect to the change in asthma.

The functional status of patients was determined during an acute attack of asthma requiring medical intervention. Patients were recruited during two months from general practice: all 28 patients consulting for an acute asthma attack were invited to take part: four refused or were withdrawn from follow up. Matched control patients with asthma, not suffering from an acute attack were selected from the practice file. Patients were investigated directly after the initial intervention and exactly 14 days later: respiratory symptoms, peak expiratory flow rates and functional status were recorded. In all cases the intervention resulted in the relief of symptoms and a return of peak expiratory flow to the normal predicted range for age, sex and height. After the 14 days, patients had no longer evidence of an exacerbation of their asthma. During the attack, there were indications of reduced physical and psychological functions, and reduced daily and social activities. A difference was found in the functional profile of asthmatics with an asthma attack and asthmatics without an asthma attack. After 14 days, the functional status of all the dimensions had improved. There was no evident correlation to the change in functional status and peak expiratory flow rates. An asthma attack hampers the patient in his daily functioning--not only physically, but also in social functioning and feelings. There are indications that the recuperation in terms of functioning takes longer than the symptoms to disappear or the peak expiratory flow to return to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological

"Asthma Alley": a space clustering study of asthma in Brooklyn, New York City.

A certain section of the borough of Brooklyn has sometimes been referred to as "Asthma Alley," expressing a feeling that this area in Brooklyn shows a markedly higher rate of asthma than adjacent areas. This study describes an epidemiologic method developed to determine whether the popular perception of spatial clustering of cases reflects reality. The spatial distribution of respiratory visits to the emergency room is taken as a reference against which clustering of asthma visits is compared, on the assumption that it is a good measure of the proportion of people in that area that make use of the emergency room facilities. From approximately 9,000 visits for asthma during the study period we were able to show that: (1) the differences in distribution of asthma cases among the health areas of Brooklyn are statistically significant; and (2) the health areas that show an excess of asthma visits lie along a belt east of the two hospitals and coincide with the popular impression of the location of "Asthma Alley."

Adult

Bronchial asthma in the Nigerian savanna region. A clinical and laboratory study of 106 patients with a review of the literature on asthma in the tropics.

One hundred and six asthma patients were studied in Zaria in the Nigerian savanna region. This group resembled hospital attenders in general in containing a disproportionately large number of immigrants from southern Nigeria and students undergoing higher education. Childhood asthma was rare. Asthma started after the age of 19 years in 69 per cent of patients. Twenty-seven per cent gave a history of rhinitis but none had had eczema. Twenty-two per cent gave a family history of asthma. Cutaneous hypersensitivity to house dust supported by a history of attacks being precipitated by dust was found in 41 per cent of patients. Asthma was worst in the rainy season in 45 per cent of patients. Mites were found in mattress dust samples; the mean count was 243 mites per g dust; Dermatophagoides farinae formed 86-6 per cent of the total mite population. The variability of airways obstruction averaged 50 per cent of maximum values for forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF). The median severity of airways obstruction measured as FEV1/VC per cent was four standard deviations below predicted normal. Eighty-seven per cent of patients were positive to prick skin tests with one or more allergens. The commonest reactions were to house dust (58 per cent), house dust mite (45 per cent) and Dermatophagoides farinae (44 per cent). Fifty-one per cent of a group of controls were also positive on skin testing but the pattern of responses was different from the asthmatic patients. This high proportion of reactors is explained by high allergen load. Serum IgE levels were lower in the asthmatics than in a group of healthy controls who showed the very high levels characteristic of some African populations. We suggest that the controls were protected from atopic disease by developing high blocking levels of non-specific IgE, perhaps in response to gut helminths. The clinical pattern of asthma in Zaria is compared with other countries in the tropical and temperate zones. The particular problems of treating asthma in developing tropical countries are discussed.

Adolescent

[Clinical studies on steroid-dependent intractable asthma. Comparison between early and late onset of asthma].

The various components making for severe intractable asthma were clinically and allergo-immunologically studied in 90 patients with bronchial asthma, by comparison between early onset and late onset groups. 1. In the early onset asthma group, cases with low serum IgE levels showed a stronger tendency toward severe intractable asthma. 2. Late onset asthma cases with negative skin tests and negative specific IgE antibodies to house dust tended more often to be severe intractable cases. 3. There was no correlation between sensitization by specific antigens (house dust and Candida), especially Candida, and a tendency toward severe intractable asthma. 4. Severe intractable asthma might be caused by bronchospasm in cases under 30 years of age, by bronchospasm plus hypersecretion in cases between 31 and 40 years of age, and by bronchospasm plus bronchiolar obstruction in cases over 40 years of age.

Adolescent