The relationship of plasma histamine to the activity of bronchial asthma

Venous plasma histamine levels were measured in 60 asthmatic subjects in order to investigate the role of histamine in naturally occurring asthmatic episodes. The patients were divided into 3 groups of 20 according to the degree of disease activity. Group A consisted of asthmatic patients with severe exacerbations. Flow/volume curves demonstrated a forced expiratory volume in 1 sec to forced vital capacity ratio ($\text{FEV}{}_1\text{FVC}$) of less than 55% and a maximum expiratory flow at 50% of FVC (MEF₅₀) of less than 1.0 L/sec. Asthmatics in group B were in partial remission. The patients in this group had $\text{FEV}{}_1\text{FVC}$ ratios between 55% and 75% and MEF₅₀ values between 1.0 and 4.0 L/sec. The remaining asthmatic patients (group C) were in complete remission. They were asymptomatic and had normal physical examinations and flow/volume curves. Venous plasma histamine levels were also measured in 50 normal control subjects (group D). Every asthmatic subject in group A had plasma histamine above 1.25 ng/ml (mean, 1.9 ng/ml ± 0.5). Only 3 asthmatic patients in group B and 3 in group C had venous plasma histamine levels greater than 1 ng/ml. None of the normal subjects in group D had plasma histamine above 1 ng/ml. These data show a relationship between spontaneously occurring asthmatic attacks and elevated plasma histamine and support previous studies suggesting that histamine may play a role in the mediation of bronchial asthma.     

Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma

In aspirin-intolerant subjects, adverse bronchial and nasal reactions to cyclooxygenase (COX) inhibitors are associated with over-production of cysteinyl-leukotrienes (cys-LTs) generated by the 5-lipoxygenase (5-LO) pathway. In the bronchi of patients with aspirin-intolerant asthma, we previously linked cys-LT over-production and aspirin hyper-reactivity with elevated immunoexpression in eosinophils of the terminal enzyme for cys-LT production, LTC4 synthase. We investigated whether this anomaly also occurs in the nasal airways of these patients. Immunohistochemical expression of 5-LO and COX pathway proteins was quantified in nasal polyps from 12 patients with aspirin-intolerant asthma and 13 with aspirin-tolerant asthma. In the mucosa of polyps from aspirin-intolerant asthmatic patients, cells immunopositive for LTC4 synthase were four-fold more numerous than in aspirin-tolerant asthmatic patients (p=0.04). There were also three-fold more cells expressing 5-LO (p=0.037), with no differences in 5-LO activating protein (FLAP), COX-1 or COX-2. LTC4 synthase-positive cell counts correlated exclusively with mucosal eosinophils (r=0.94, p<0.001, n=25). Co-localisation confirmed that five-fold higher eosinophil counts (p=0.007) accounted for the increased LTC4 synthase expression in polyps from aspirin-intolerant asthmatic patients, with no alterations in mast cells or macrophages. Within the epithelium, increased counts of eosinophils (p=0.006), macrophages (p=0.097), and mast cells (p=0.034) in aspirin-intolerant asthmatic polyps were associated only with 2.5-fold increased 5-LO-positive cells (p<0.05), while the other enzymes were not different. Our results indicate that a marked over-representation of LTC4 synthase in mucosal eosinophils is closely linked to aspirin intolerance in the nasal airway, as in the bronchial airways.     

Exhaled eicosanoids following oral aspirin challenge in asthmatic patients

BACKGROUND: Biochemical analysis of expiratory breath condensate is an emerging non-invasive technique for assessment of airway inflammation. OBJECTIVE: We wondered whether application of expiratory breath condensate could facilitate diagnosis of aspirin-intolerant asthma and reproduce eicosanoids mediators' abnormalities described in this disease. METHODS: We measured prostaglandins (PGs) E(2), F(2 alpha), 9 alpha 11 beta F(2) and iso-F(2) by gas-chromatography/mass-spectrometry and cysteinyl leukotrienes (cys-LTs) by radioimmunoassay in breath condensates of asthmatic patients undergoing oral aspirin challenge. Fourteen patients with aspirin-induced asthma and 20 aspirin-tolerating asthmatics, most of them on chronic inhaled corticotherapy, were studied and compared with 10 healthy subjects. Additionally, plasma 9 alpha 11 beta PGF(2), the metabolite of PGD(2) and urinary leukotriene (LT) E(4) were measured before and following the challenge. RESULTS: At baseline, PG did not differ between the groups, except for lower 9 alpha 11 beta PGF(2) in aspirin-intolerant asthma. Their concentrations were not changed by the challenge. Breath condensate cys-LTs were similar in the groups studied at base, and after aspirin challenge increased only in aspirin-intolerant patients. Elevated baseline urinary LTE(4) and its further increase following aspirin challenge was highly diagnostic for aspirin-intolerant asthma. The discriminatory value of cys-LTs increase in breath condensates was lower (72.8%) than either basal (99%) or post-challenge increase (94%) of urinary LTE(4). CONCLUSIONS: In asthmatic patients on chronic corticotherapy measurement of urinary LTE(4) excretion rather than cys-LTs in breath condensate is of greater value for diagnosis of aspirin hypersensitivity.     

Tryptase and histamine release during aspirin-induced respiratory reactions

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.     

Allergen-induced increase in non-allergic bronchial reactivity

Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV₁ fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV₁ fall) in four, and equivocal late asthmatic responses (5–11% FEV₁ fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.     

Recurrent nocturnal asthma after bronchoprovocation with Western Red Cedar sawdust: association with acute increase in non-allergic bronchial responsiveness

Recurrent nocturnal asthma following a single exposure to Western Red Cedar sawdust was documented by measurements of peak flow rates in two sensitized subjects. The nocturnal asthma followed a dual asthmatic response in the first subject and a late (non-immediate) asthmatic response in the second. Both subjects developed a 10-fold reduction in the dose of histamine required to decrease the FEV₁ by 20%. This cedar-induced increase in non-specific bronchial reactivity was maximal at the time of the recurrent nocturnal asthma, and persisted after nocturnal asthma had ceased and after FEV₁ had returned to normal. We hypothesize that the enhanced non-specific bronchial reactivity which occurs following late asthmatic responses to bronchial challenge is the cause of recurrent nocturnal asthma following single exposure to a sensitizing agent.     

Plasma histamine and bronchial reactivity in allergic asthma

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic asthmatic patients have yielded controversial results. We therefore measured plasma histamine and bronchial reactivity in 30 nonsmoker volunteers taking no medication. Eleven were normal subjects; 19 were stable, mildly allergic asthmatic patients. Venous blood was taken to measure blood cells and basal plasma histamine by radioimmunoassay. After blood sampling, all subjects underwent a measurement of PC₂₀M (concentration of methacholine causing a 20% fall in FEV₁). Mean plasma histamine levels were 0.21 ± 0.1 ng/ml and 0.44 ± 0.3 ng/ml in normal and asthmatic subjects, respectively (P<0.05). We found a significant increase of blood eosinophils and basophils in asthmatic patients, and a positive correlation between plasma histamine and circulating basophils. PC₂₀M was greater than 16 mg in normal volunteers, and mean PC₂₀M was 2.1 ± 2 mg/ml in asthmatic patients. PC₂₀M did not correlate with plasma histamine levels, but it did so negatively with blood eosinophils. The increased plasma histamine concentration in mildly atopic asthmatic patients might be a consequence of the high basophil releasability of atopies and the higher basophil counts in allergic asthma. Plasma histamine is thus unlikely to be a determinant of BHR in asthma.     

Indoor allergens and longitudinal FEV 1 decline in older adults: The Normative Aging Study

We investigated the relationship between home allergen exposure and decline in FEV₁ in 10 asthmatic and 30 randomly selected, age-matched, nonasthmatic participants in the Normative Aging Study. We defined asthma as subject-reported wheezing apart from colds, with either a physician's diagnosis of asthma or a methacholine PD₂₀ FEV₁ of 8.6 μmol or less. We examined the relationship between the annual decline in FEV ₁ and the concentrations of the cockroach (Blattella germanica) allergens Bla g 1 and Bla g 2, the dust mite (Dermatophagoides pteronyssinus and Dermatophagoides farinae) allergens Der p 1 and Der f 1, and the cat (Felis domesticus) allergen Fel d 1 in house dust specimens. Bla g 1 (–79.8 ml/yr, p = 0.0006) and Bla g 2 (–40.81 ml/yr, p = 0.0004) were significant predictors of decline in FEV₁ after adjustment for age, smoking, and baseline FEV₁. These results were unchanged after elimination of the asthmatic subjects from the analysis. We conclude that cockroach allergen levels in homes is a risk factor for accelerated decline in FEV₁ independent of airway responsiveness. (J Allergy Clin Immunol 1998;101:720–5.)     

Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by progressive sinusitis, nasal polyposis, and asthma that begins and continues in the absence of exposure to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Cross-sensitivity to all NSAIDs that inhibit cyclooxygenase-1 (COX-1) occurs in these individuals. Reactions to aspirin and NSAIDs in patients with AERD are largely due to inhibition of COX-1. Despite accumulating data on the safety of COX-2 selective inhibitors in AERD, concern still remains that high doses of a COX-2 inhibitor may be sufficient to induce a cross-reaction. OBJECTIVE: To determine whether high-dose rofecoxib cross-reacts in patients with AERD and asthma. METHODS: Sixty asthmatic patients underwent blinded placebo-controlled oral challenges with 50 mg of rofecoxib. Aspirin sensitivity was subsequently confirmed in all patients with the use of single-blinded aspirin challenges. RESULTS: None of the 60 patients experienced any symptoms, changes in nasal examination results, or declines in lung function during rofecoxib challenge. All 60 patients experienced respiratory reactions to aspirin challenge, with a mean provoking dose of 57 mg. The exact 1-sided 95% confidence interval for the underlying probability of 50 mg of rofecoxib inducing respiratory cross-reactions in patients with AERD is 0 to 0.05, or 0% to 5%. CONCLUSIONS: These results confirm the lack of cross-reactivity of aspirin and the highly selective COX-2 inhibitors in AERD. We suggest that it is time for the labeling of highly selective COX-2 inhibitors to reflect these data and for the warning that patients with AERD in particular and asthmatic patients in general avoid selective COX-2 inhibitors to be removed.     

Emotions and respiratory function in asthma: A comparison of findings in everyday life and laboratory

Objectives. The present study examined the influence of emotions on the respiratory function in asthmatic and non‐asthmatic individuals in everyday life and the relationship to emotion‐induced respiratory changes in the laboratory. Methods. Affective states were induced in 10 asthmatic and 10 non‐asthmatic participants by viewing affective picture series of either a pleasant, neutral, or unpleasant valence, while airway resistance (R_aw) was measured with whole body plethysmography. Following this, individuals measured their mood, forced expiratory volume in the first second (FEV₁), peak expiratory flow (PEF), physical activity, and medication use for 21 days with an electronic diary, which included a respiratory self‐measurement device. Strong pleasant and unpleasant mood episodes were extracted from the diaries and compared with neutral affective states. Results. Asthmatic patients showed increases of R_aw after unpleasant and pleasant emotional stimulation in the laboratory, which was only found after a pleasant stimulation in non‐asthmatic participants. In everyday life, no group differences were obtained. Episodes of strong unpleasant mood states were associated with decreases in PEF, whereas in contrast to the laboratory assessment, pleasant mood was associated with increases in PEF. Results for FEV₁ were comparable, but non‐significant. Physical activity and medication use did not vary systematically between affective episodes. PEF showed no significant relationship with R_aw. Conclusions. Unpleasant mood is associated with decreased respiratory function in asthmatic patients in everyday life and in laboratory assessments, whereas effects of pleasant mood states are inconsistent. Pulmonary responses to laboratory‐induced emotional conditions are not predictive of airways reactivity during daily life.     

A comparison of spirometric measurements in allergen bronchial challenge testing

We compared the usefulness of several spirometric measurements in detecting asthmatic reactions after allergen bronchial challenge in fourteen asthmatic children. All of the children had a history suggesting mite-induced asthma and eleven had a 3 mm or larger diameter weal on prick testing with Dermatophagoides farinae extract. On bronchial challenge testing with dilutions of this extract twelve children had an early asthmatic reaction and nine had a late asthmatic reaction. In decreasing order of sensitivity for detecting the early asthmatic reaction the tests ranked as follows: FEV₁, FEF_50%, FEF_25-75%, PEFR and FVC. For the late asthmatic reaction the order was FEF_50% FEV₁, FEF_25-75%, PEFR and FVC. No single test identified all the early or all the late reactions but the FEV₁, a test useful for indicating large airways obstruction, when combined with the FEF_25-75%, a test influenced by small airways obstruction, detected all early and late asthmatic reactions. The FEF_50%, was a sensitive test but was the only one to become falsely positive. It became falsely positive in four patients. Although the FEV₁, was the most useful single test the results suggest that it is, by itself, an inadequate indicator of the asthmatic reaction and that it should be used with the FEF_25-75%, to ensure the detection of all asthmatic reactions induced by allergen bronchial challenge testing.     

Comparison of responses to pollen extract in subjects with allergic asthma and nonasthmatic subjects with allergic rhinitis

We compared pulmonary responses with inhaled pollen-antigen extract in eight subjects with allergic asthma and eight nonasthmatic subjects with allergic rhinitis. Lower respiratory tract sensitivity to antigen was determined from dose-response curves using SGaw and FEV₁ measurements to quantitate responses. We found no difference in antigen sensitivity in terms of SGaw between the two groups (p > 0.05). Hay fever subjects required almost eight times more antigen to produce a 20% fall in FEV₁, although there was considerable overlap between the two groups. After antigen challenge there were significant increases in lung volumes in asthmatic subjects (RV, +78.6%; FRC, +33.6%; TLC, +12.6%) which were not significantly different from rhinitis subjects (RV, +98.3%; FRC, +39.1%; TLC, +10.3%). Six rhinitis and five asthmatic subjects were rechallenged after pretreatment with atropine (2.5 mg aerosol). Atropine caused an initial increase in SGaw and FEV₁ but failed to alter sensitivity or volume responses in both groups. The effects of a maximum inspiration on physiologic responses to antigen were different in the two groups. Deep inspiration transiently improved SGaw and FRC toward prechallenge values in rhinitis subjects but the same maneuver had little effect in asthma subjects. Although only asthma subjects experience lower respiratory tract symptoms during periods of environmental pollen exposure, these two groups of subjects were indistinguishable on the basis of their immediate responses to inhaled antigen. This suggests that asthmatic symptoms during the pollen season are unrelated to the immediate effects of allergic reactions to pollen. This also suggests that these bronchial challenge responses represent a localized anaphylactic reaction, whereas naturally occurring asthma during the pollen season may represent a syndrome of increased airways reactivity which is perhaps related to antigen exposure.     

Rapid FEV1/FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population

BackgroundForced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV₁/FVC decline rate in the Korean general population and to identify whether rapid FEV₁/FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality.MethodsWe evaluated individuals aged 40−69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV₁/FVC decline rate, the most negative FEV₁/FVC change (1^st quartile of annual FEV₁/FVC decline rate) was classified as rapid FEV₁/FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV₁/FVC decline.ResultsThe annual FEV₁/FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV₁/FVC decline than in those with non-rapid FEV₁/FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932–2.324). Rapid FEV₁/FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105–1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089–1.680).ConclusionThe annual FEV₁/FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV₁/FVC decliners.     

Studies of the effects of inhaled magnesium on airway reactivity to histamine and adenosine monophosphate in asthmatic subjects

Background Magnesium is a cation with smooth muscle relaxant and anti-inflammatory effects and may therefore have a role in the therapy of asthma. Several studies have investigated the effects of intravenous magnesium in acute or stable asthma, but little is known about the effects of inhaled magnesium. Objective To measure the effects of a single inhaled nebulized dose of 180 mg magnesium sulphate on airway reactivity to a direct-acting bronchoconstrictor (histamine) and an indirect-acting bronchoconstrictor (adenosine monophosphate [AMP]) in asthmatic subjects. Objective Two separate randomized, double-blind, placebo-controlled crossover studies, each involving 10 asthmatic subjects. In the histamine study, airway reactivity to histamine was measured and lung function allowed to recover spontaneously over 50 min before administering nebulized magnesium sulphate or saline placebo. Airway reactivity to histamine was then measured at 5 and 50 min. In the AMP study, a single measurement of airway reactivity was made 5 min after magnesium or placebo. Results In the histamine study, the provocative dose required to reduce FEV₁ by 20% (PD₂₀FEV₁) was significantly lower after magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22–1.82) doubling doses at 5 min (P= 0.018), and 1.0 (0.3–1.7) doubling doses at 50 min (P= 0.01). In the AMP study, PD₂₀FEV₁ was also significantly lower at 5 min after magnesium than after saline, by 0.64 (0.12–1.16) doubling doses (P= 0.023), though this difference was not statistically significant after adjustment for differences in baseline FEV₁ on the two study days. Conclusions Inhaled magnesium did not protect against the effects of these direct and indirect bronchoconstrictor stimuli in subjects with asthma, and may have increased airway reactivity to histamine.     

Effect of disodium cromoglycate on asthmatic reactions to alcoholic beverages

Eleven asthmatic patients with a history of asthma with or without rhinitis following the ingestion of alcoholic drinks were challenged by oral ingestion of the suspected drink, and some with equivalent amounts of ethyl alcohol. Asthma was provoked in six cases, four having falls in the FEV₁ of more than 15%. Three of the latter studied in detail gave immediate asthmatic reactions to the alcoholic beverage, but not to the ethyl alcohol tested by oral ingestion, and in one case by administration through a naso-gastric tube. Pre-treatment by inhalation of disodium cromoglycate inhibited the asthmatic reactions to the alcoholic beverages.     

Aspirin-sensitive asthma: Tolerance to aspirin after positive oral aspirin challenges

Two aspirin-sensitive asthmatic patients underwent oral aspirin challenges for investigative purposes. Following the expected respiratory reaction to aspirin, the patients became refractory to the further adverse effects of aspirin. Additionally they began taking 325 mg aspirin per day, and after 6 and 8 mo aspirin dosage was increased to 650 mg per day. We have noted an improvement in their rhinitis and asthma during this open drug trial. Furthermore, maintenance systemic corticosteroids have been reduced in one patient and discontinued in the other without a decline in lung function values. If these initial observations are found in a larger number of aspirin-sensitive asthmatic patients, changes in our understanding of the pathogenesis of rhinosinusitis-asthma-aspirin syndrome would follow, and treatment for such asthmatic patients might be improved.     

Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease

BACKGROUND: In patients with aspirin-exacerbated respiratory disease (AERD), pretreatment with asthma controller medications (leukotriene modifiers, inhaled or systemic corticosteroids, and salmeterol) partially modifies the severity of aspirin-induced asthmatic reactions. OBJECTIVE: A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization. METHODS: Ten patients with rhinosinusitis, nasal polyps, and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs. All underwent baseline oral aspirin challenges and had typical respiratory reactions. They were then randomized to receive tacrolimus (0.1 mg/kg weight; 8 patients) or placebo (2 patients) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin. In addition, respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded, analyzed, and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences. RESULTS: Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD, and in the other 3 patients did not block higher doses of aspirin. The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD, and there were no significant differences. CONCLUSIONS: Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished.     

Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber

Allergen-induced late asthmatic responses are associated with an increase in bronchial responsiveness to histamine. We have examined the relationship between the magnitude of the late asthmatic response and the magnitude and duration of increased histamine responsiveness. Allergen inhalation tests were carried out in 12 asthmatic subjects to induce a mild early asthmatic response (16% to 40% reduction in FEV₁ in the first hour after allergen inhalation); the response was followed over 8 hr to identify the occurrence and magnitude of any late asthmatic response (maximum fall in FEV₁ from baseline between 3 and 8 hr). The provocation concentration of histamine causing a decrease in FEV₁ of 20% (PC₂₀) was measured before and after inhalation of allergen. The magnitude of decrease in PC₂₀ correlated with the magnitude of the late asthmatic response as measured by the percent fall in FEV₁ (r = 0.8, p < 0.002). The duration of decrease in PC₂₀ was from 2 to 74 days and this also correlated with the magnitude of the late response (r = 0.53, p < 0.05). Total lung capacity (TLC), residual volume (RV), FEV₁, maximal expiratory flow-volume curves (on air and He-O₂), and histamine responsiveness were also measured before and at intervals after allergen inhalation. Four of seven subjects still had a reduction in PC₂₀ when the TLC, RV, FEV₁, maximal expiratory flow-volume rates on air (V?₅₀air) and He-O₂ (V?₅₀He-O₂) (measured at an absolute volume corresponding plus 50% of control vital capacity) and ratio of V?₅₀He-O₂ to V?₅₀air were back t preallergen inhalation levels. In two of these subjects volume of isoflow was also back to ±10% of preallergen inhalation levels when the PC₂₀ was still significantly reduced. The results suggest that allergen-induced late asthmatic responses can be associated with an increase in bronchial responsiveness to histamine by mechanisms other than a reduction in baseline airway caliber alone.     

Aspirin-sensitive rhinosinusitis/asthma: spectrum of adverse reactions to aspirin

In order to determine the types of respiratory responses observed during aspirin-induced reactions, 50 consecutive asthmatic patients with a history of aspirin sensitivity underwent prospective oral aspirin challenges between 1979 and 1981. Oral aspirin challenges produced 36 asthmatic responses (33 combined with rhinitis and three purely asthmatic) and six acute rhinoconjunctivitis responses (three combined with mild asthma and three purely rhinoconjunctivitis) but failed to stimulate any reaction in eight patients. The results produced by these challenges were then compared with results recorded during additional aspirin challenges in 28 of these patients, performed after the index challenge in 1979-1981 in 26 patients and in the case of two patients before 1979. The type of respiratory response to aspirin varied significantly in 11 (39%) of the 28 patients and included disappearance of aspirin reactivity in four patients.