Cigarette smoking is associated with high prevalence of chronic rhinitis and low prevalence of allergic rhinitis in men.

BACKGROUND: The harmful effects of tobacco smoke on human health, including respiratory health, are extensive and well documented. Previous data on the effect of smoking on rhinitis and allergic sensitization are inconsistent. We sought to investigate how smoking correlates with prevalence of allergic and chronic rhinitis among adults in Sweden. METHODS: The study population comprised 27 879 subjects derived from three large randomly selected cross-sectional population surveys conducted in Sweden between 2006 and 2008. The same postal questionnaire on respiratory health was used in the three surveys, containing questions about obstructive respiratory diseases, rhinitis, respiratory symptoms and possible determinants of disease, including smoking habits. A random sample from one of the cohorts underwent a clinical examination including skin prick testing. RESULTS: Smoking was associated with a high prevalence of chronic rhinitis in both men and women and a low prevalence of allergic rhinitis in men. These associations were dose dependent and remained when adjusted for a number of possible confounders in multiple logistic regression analysis. Prevalence of chronic rhinitis was lowest in nonsmokers and highest in very heavy smokers (18.5% vs 34.5%, P < 0.001). Prevalence of sensitization to common airborne allergens was lower in current smokers (25.9%, P = 0.008) and ex-smokers (28.2%, P = 0.022) than in nonsmokers (38.5%). CONCLUSION: We found that smoking was associated with a high prevalence of chronic rhinitis in both sexes and a low prevalence of allergic rhinitis in men. The associations were dose dependent and remained when adjusting for several possible confounders.

Has the increase in the prevalence of asthma and respiratory symptoms reached a plateau in Stockholm, Sweden?

SETTING: An increase in the prevalence of asthma has previously been reported worldwide. However, the current trend is debatable. OBJECTIVE: To assess changes in the prevalence of asthma and respiratory symptoms in a defined study area in Stockholm, Sweden, using identical methods. DESIGN: A questionnaire was sent by mail in 1996 and 2007 to randomly selected subjects aged 20-69 years. On both occasions, 8000 subjects received the questionnaire, with response rates of 72% and 68%, respectively. Questions on asthma, respiratory symptoms, asthma medication and possible determinants were included. Logistic regression analysis was used to assess determinants. RESULTS: Ever asthma increased from 8.7% in 1996 to 11.0% in 2007 and physician-diagnosed asthma from 7.6% to 9.3%. The proportion of asthma patients reporting one to two symptoms increased by 14% during the study period. There were few significant changes in the prevalence of respiratory symptoms: wheeze in the previous 12 months (15.9-17.3%), wheezing with breathlessness apart from cold (3.2-4.1%) and recurrent wheeze (8.3-6.8%). There was no major difference in the risk factor pattern between the surveys. CONCLUSION: An increase in the prevalence of asthma with few symptoms as well as an unchanged prevalence of symptoms was demonstrated, which may indicate a change in diagnostic practices.

An index for breathlessness and leg fatigue.

The features of perceived symptoms causing discontinuation of strenuous exercise have been scarcely studied. The aim was to characterize the two main symptoms causing the discontinuation of heavy work in healthy persons as well as describe the growth of symptoms during exercise. Breathlessness (b) and leg fatigue (l) were assessed using the Borg CR10 Scale and the Borg CR100 (centiMax) Scale, during a standardized exercise test in 38 healthy subjects (24-71 years). The b/l-relationships were calculated for terminal perceptions (ERI(b/l)), and the growth of symptoms determined by power functions for the whole test, as well as by growth response indexes (GRI). This latter index was constructed as a ratio between power levels corresponding to a very strong and a moderate perception. In the majority (71%) of the test subjects, leg fatigue was the dominant symptom at the conclusion of exercise (P<0.001) and the b/l ratio was 0.77 (CR10) and 0.75 (CR100), respectively. The GRI for breathlessness and leg fatigue was similar, with good correlations between GRI and the power function exponent (P<0.005). In healthy subjects, leg fatigue is the most common cause for discontinuing an incremental exercise test. The growth functions for breathlessness and leg fatigue during work are, however, almost parallel.

Repeated exposure to organic material alters inflammatory and physiological airway responses.

Farmers and smokers are repeatedly exposed to airborne organic material. We hypothesised that farmers and smokers show altered airway responses to inhaled organic, pro-inflammatory agents. A total of 11 farmers, 12 smokers and 12 controls underwent lipopolysaccharide (LPS) bronchial challenge and spent 3 h in a pig barn. Lung function, exhaled nitric oxide and bronchial responsiveness were assessed and nasal lavage fluid and induced sputum were also collected. Symptoms and body temperature were recorded before and after exposures. Following exposure to the pig barn, bronchial responsiveness, exhaled nitric oxide, sputum interleukin (IL)-6, nasal lavage cell count and IL-8 were increased to a greater extent in controls compared to farmers. The sputum IL-6 response was also attenuated in farmers after LPS challenge. The response shown by smokers following exposure to the pig barn was similar to that of controls regarding measurements of exhaled nitric oxide, IL-8 in nasal lavage and IL-6 in sputum, but more similar to farmers concerning bronchial responsiveness and the cell numbers present in nasal lavage. Sputum IL-8 showed a greater increase in smokers than in the other groups following LPS challenge. We conclude that individuals who are repeatedly exposed to organic material develop an adaptation to the effects of acute exposure to inhaled organic material.

Saliva is one likely source of leukotriene B4 in exhaled breath condensate.

Leukotriene (LT)B4 in exhaled breath condensate (EBC) has been reported to be elevated in airway inflammation. The origin of leukotrienes in EBC is, however, not established. The aims of this study are to measure LTB4 levels in EBC collected in two challenges characterised by a strong neutrophilic airway inflammation and to compare LTB4 levels in EBC with levels in sputum and saliva. LTB4 and alpha-amylase were measured in EBC from 34 healthy subjects exposed in a pig confinement building or to a lipopolysaccharide provocation. These markers were also measured in induced sputum in 11 of the subjects. For comparison, LTB4 and alpha-amylase were measured in saliva from healthy subjects. Only four out of 102 EBC samples had detectable LTB4 (28-100 pg x mL(-1)). alpha-amylase activity was detected in the LTB4-positive samples. In contrast, LTB4 was detected in all examined sputum supernatants in the same study (median 1,190 pg x mL(-1)). The median LTB4 level in saliva was 469 pg x mL(-1). High levels of leukotriene B4 in saliva and the presence of leukotriene B4 in exhaled breath condensate only when alpha-amylase was detected, indicate that leukotriene B4 found in exhaled breath condensate is the result of saliva contamination. As leukotriene B4 was consistently present in sputum supernatants, exhaled breath condensate may be inappropriate for monitoring airway leukotriene B4.

Exhaled nitric oxide and bronchial responsiveness in healthy subjects exposed to organic dust.

Inhalation of organic dust from swine houses causes an intense inflammatory reaction in the respiratory tract, and increased bronchial responsiveness to methacholine in healthy subjects. The aims of the present study were to investigate whether exhaled nitric oxide (NO) is a marker of the inflammation caused by exposure to organic dust (swine dust), whether there is a relationship between an increase in exhaled NO and bronchial responsiveness, and also whether wearing a half-mask influences the airway reaction (assessed by exhaled NO) and the increased bronchial responsiveness. Thirty-three healthy nonatopic, nonsmoking subjects were exposed during 3 h of light work in a swine confinement building. Eleven of the subjects were wearing a half-mask and 22 were unprotected. Lung function, bronchial responsiveness and exhaled NO were measured before and after exposure. The provocative concentration causing a 20% fall in forced expiratory volume in one second fell by 2.7 (2.1-4.1) (median (25th-75th percentiles)) doubling concentration steps in subjects without a half-mask and by 1.5 (0.9-2.9) doubling concentration steps in subject wearing a mask. Exhaled NO increased from 7.5 (5.7-13.7) parts per billion (ppb) before to 13.4 (10.5-17.5) ppb after exposure in the unprotected group and was unaltered (8.3 (6.1-14.1) to 8.6 (6.6-14.6) ppb) in the group wearing a half-mask. There was no correlation between NO increase and provocative dose causing a 20% fall in the forced expiratory volume in one second decrease. In conclusion, bronchial responsiveness and exhaled nitric oxide increased after exposure to a swine confinement facility. Half-mask abolished the increase in exhaled nitric oxide levels, but influenced the increase in bronchial responsiveness to a minor extent. These results indicate that these two outcome measures reflect different aspects of airway inflammation induced by exposure to a farming environment.

Effect of deep inhalations after a bronchial methacholine provocation in asthmatic and non-asthmatic subjects.

Deep inhalations cause a transient relaxation of the peripheral airways smooth muscles in non-asthmatic subjects. It has been claimed that the airway response to deep inhalations may be different in asthmatic subjects in whom deep inhalations should rather cause bronchoconstriction. The aim of the present study was to find out whether deep inhalations discriminate between asthmatic and non-asthmatic subjects with pre-constricted airways, using a methacholine provocation test protocol with deep inhalations following the last dose of methacholine. In 164 adults, a methacholine provocation was performed. Directly after the FEV1 measurement at the highest metacholine concentration, the subjects took one deep breath and another three deep inhalations 20 s later. One minute after the inhalation of the highest concentration FEV1 was measured twice. Thirty-three asthmatics PD20FEV1 = 0.24 mg (0.13-0.39) (median, 25-75th 75th percentiles) and 131 non-asthmatics PD20FEV1 = 2.05 mg (0.72-10.1) participated. The mean maximal decrease in FEV1 after the provocation test was 36% in the asthmatics and 27% in the non-asthmatics. Corresponding values after the deep inhalations were 18% in the asthmatics and 12% in the non-asthmatics. In conclusion, deep inhalations attenuate the methacholine-induced bronchoconstriction in both asthmatic and non-asthmatic subjects. Thus, the effect of deep inhalations did not discriminate between asthmatic and non-asthmatic subjects.

Comparison of airway conductance and FEV(1) as measures of airway responsiveness to methacholine. Discrimination of small differences in bronchial responsiveness with Gaw and FEV(1).

When defining bronchial responsiveness in healthy, non-asthmatic, subjects exposed in different working situations, it is not clear whether different outcome measures yield similar results. Therefore, the concentration and dose of methacholine that caused a 20% decrease in forced expiratory volume in 1 s (FEV(1)) (PC20(FEV(1)) and PD20(FEV(1))), the corresponding change in Gaw and the relationship between the dose-response slope (DRS) for FEV(1) and Gaw was studied in different working populations and healthy control subjects (n=1038). The two outcome measures were compared in groups of subjects in whom differences in bronchial responsiveness could be anticipated [atopics (n=72) and non-atopics (n= 207) and subjects exposed (n=54) and not exposed (n=32) to saw dust]. A bronchial challenge was also made before and after exposure in a swine confinement building, an exposure known to increase bronchial responsiveness (n=37). PD20(FEV(1)) was 1.7 mg in atopics and 4.9 mg in non-atopics, 7.1 mg in saw dust exposed and >20 mg in non-exposed subjects and 5.3 mg before and 0.79 mg after exposure to organic dust. There was a correlation between DRS(FEV(1)) and DRS(Gaw), r=0.87 (P<0.001). In subjects who were highly sensitive to methacholine a 20% change in FEV(1) corresponded to <40% change in Gaw, while a 20% decrease in FEV1 corresponded to none or a minor decrease in Gaw in subjects with less methacholine-sensitive airways. The ability to detect differences in bronchial responsiveness between groups, or to detect changes in bronchial responsiveness following exposure was approximately the same for FEV(1) and Gaw. The reproducibility was similar for both variables and a second measurement was within one doubling of the methacholine concentration of the first provocation in approximately 95% of all measurements (n=41). In conclusion, with our methacholine provocation method, FEV(1) and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness in healthy subjects.

Sodium cromoglycate attenuates pulmonary inflammation without influencing bronchial responsiveness in healthy subjects exposed to organic dust.

BACKGROUND: Inhalation of organic dust from a pig house induces airway inflammation and increases bronchial responsiveness to methacholine in healthy subjects. OBJECTIVE: To study whether sodium cromoglycate influences the airway inflammatory reaction and the increase in airway responsiveness induced by inhalation of organic dust. METHODS: Bronchoalveolar and nasal lavages, and bronchial methacholine challanges were performed and blood samples were drawn in 32 healthy subjects before and after exposure to dust in a pig farm. Sodium cromoglycate was inhaled (20 mg, twice a day) and administered intranasally (5.2 mg, twice a day) by 16 and a corresponding placebo was given to the other 16 healthy controls for two weeks prior to exposure. RESULTS: Exposure induced a significant increase in inflammatory cells and soluble components (pro-inflammatory cytokines, inflammatory mediators) in bronchoalveolar and nasal lavage fluid in both groups. The increase in neutrophils, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha as well as myeloperoxidase and soluble intracellular adhesion molecule (ICAM)-1 in bronchoalveolar lavage (BAL) fluid was significantly reduced by treatment with sodium cromoglycate. Although sodium cromoglycate inhalation largely influenced a variety of inflammatory indices in bronchoalveolar lavage fluid it had no effect on the increase in bronchial responsiveness to methacholine. CONCLUSION: Sodium cromoglycate alters the airway inflammatory response to inhaled organic dust without influencing the dust-induced increase in bronchial responsiveness to methacholine.

Different response to doubling and fourfold dose increases in methacholine provocation tests in healthy subjects.

RATIONALE: In a modified methacholine provocation test that was used to study changes in airway responsiveness to occupational irritants or sensitizers in healthy subjects, two protocols were used: a long protocol (doubling methacholine concentrations between dose steps) or a short protocol (fourfold increases in concentration). This modified methacholine provocation allows measurements of the provocative dose causing 20% decrease in FEV(1) (PD(20)) in a high proportion of a normal population. METHODS: The distribution of PD(20) was investigated in healthy nonatopic men without history of allergy or asthma symptoms using the long protocol (n = 101) or the short protocol (n = 309). In addition, 30 healthy subjects underwent methacholine provocation tests using both protocols. RESULTS: PD(20) was defined in 79% of subjects with the long protocol and in 48% of subjects with the short protocol. The provocative concentration of methacholine causing a 20% decline in FEV(1) (PC(20)) and PD(20) were significantly lower using the long protocol: long-protocol PC(20) (median [25th to 75th percentile]), 19.9 mg/mL (3.9 to > 32 mg/mL) compared with short-protocol PC(20), > 32 mg/mL (8.7 to >32 mg/mL; p < 0.0001); long-protocol PD(20), 4.2 mg (1.6 to 20 mg) compared with short-protocol PD(20), > 13.7 (2.6 to > 13.7 mg; p = 0. 006). The differences in PD(20) using short and long protocols were confirmed in a randomized trial of 30 healthy subjects tested with both protocols. CONCLUSION: Using doubling concentrations, PC(20) and PD(20) could be defined in a higher proportion of healthy subjects than a protocol using fourfold dose increases. Furthermore, the doubling protocol results in a PD(20) estimate that is less than half the value obtained when using a protocol with fourfold concentrations between dose steps. The difference remains, whether the methacholine effect is regarded as cumulative or noncumulative. The explanation for the difference between the protocols is unclear.

The salt output of a nebulizer--a comparison between two nebulizer types.

The output of a nebulizer is generally defined as its weight loss during 1 min of nebulization. This mass output includes the weight loss due to evaporation of the solution required to moisten the dry air that is fed through the nebulizer. In order to compare results obtained from studies using different nebulizers we introduce the salt output as the amount of the solution that actually leaves the liquid phase as droplets and not by evaporation. The performance characteristics of a standard jet nebulizer (MA2) and a Sidestream jet neublizer were compared. Mass output was determined at different methacholine concentrations. Salt output was assessed by analysing the remaining salt in the nebulizers after 1 min of nebulization. Overall system performance in terms of forced expiratory volume in 1 sec (FEV1) reduction after 1 min of exposure to individually selected concentrations of methacholine were studied in 15 healthy, non-smoking subjects. Both nebulizer types showed a moderate linear increase of mass output with methacholine concentration. The efficiency coefficient, the quotient between salt output and mass output, was found to be 0.93 and 0.75 for the MA2 and Sidestream nebulizer respectively. These findings were explained by differences in airflow through, and temperature inside, the nebulizers. The salt output of the nebulizers proved to be better correlated to the FEV1-reduction following methacholine inhalation than did the mass output. The relative amount of the salt output that adhered to the acrylic walls of the Sidestream nebulizer drying tower was found to be 9%. We conclude that it is more appropriate to use salt output than mass output as a nebulizer performance descriptor. The study also shows the importance of determining nebulizer system performance under conditions as similar to true provocations as possible.

Acute effects of exposure to air contaminants in a sawmill on healthy volunteers.

OBJECTIVES: To study whether air contaminants in sawmills can induce acute changes in the upper and lower airways of previously non-exposed subjects. METHODS: Nineteen healthy volunteers were examined to find the concentration of interleukin 6 (IL-6) in nasal lavage fluid and lung function before and after five hour exposure to dusts and fumes generated in a sawmill where timber from Scots pine was sawed. When exposed, the subjects had respirators with and without a particle filter. RESULTS: The median for daily time weighted average concentration of total dust for subjects with respirators without a filter was 0.13 mg/m3, which was significantly higher than the median of 0.04 mg/m3 for subjects who had respirators with a filter. The median for the concentration of IL-6 in the nasal lavage fluid increased after exposure from 0.5 to 5.9 pg/ml in subjects with respirators without a particle filter (P < 0.05). The increase of the concentration of IL-6 was significantly correlated with the dust concentration. A decrease in transfer factor of the lung was significantly correlated with daily time weighted average concentrations of terpenes. CONCLUSION: The findings suggest that healthy volunteers, exposed to air contaminants in a sawmill, show a slight inflammatory reaction. Also, the results of the study indicate the importance of decreasing the concentrations of wood dust in the work environment.

Increased bronchial responsiveness in workers sawing Scots pine.

The purpose of the present investigation was to study bronchial responsiveness and pulmonary function in Swedish sawmill workers, who are not exposed to plicatic acid, the sensitizer in red wood cedar asthma. Bronchial responsiveness, transfer factor, spirometry, and precipitating antibodies in serum against sawmill fungi were measured in 164 workers at five sawmills. The results from workers inside the sawing area (sawyers, n=59), in the trimming department (trimmers, n=66), and from other workers in the sawmill (sawyer-referents, n=39) were compared. Sawyers had higher bronchial responsiveness than referents. In 55% of the sawyers FEV1 decreased by 20% or more within the highest dose of methacholine compared with 31% of sawyer-referents and 41% of trimmers (p<0.01, sawyers/referents). Sawyers decreased 74% more in FEV1 per milligram of inhaled methacholine compared with referents (geometric means, p<0.01). The transfer test in never-smokers was 13% lower in sawyers than in trimmers (p<0.01) and 8% lower compared with sawyer-referents (nonsignificant p<0.1). Presence of precipitating antibodies was not associated with changes in pulmonary function. Some agents in the sawing area of sawmills appear to increase bronchial responsiveness and decrease diffusion capacity.

Allergic sensitization is associated with increased bronchial responsiveness: a prospective study of allergy to laboratory animals.

The purpose of this prospective study was to investigate the extent of change in bronchial responsiveness and the prognostic value of methacholine provocation in early sensitization to laboratory animals. Thirty eight laboratory technicians were studied during training (before first exposure) and after having been exposed to laboratory animals for a median 18 (range 5-33) months. On both occasions they were subjected to spirometry, bronchial methacholine challenge, skin-prick tests and blood sampling, and responded to questionnaires. Nine (24%) developed laboratory animal allergy (LAA), defined as animal work-related symptoms (n = 8), or specific immunoglobulin E (IgE) (n = 7) or both. In the LAA group, bronchial responsiveness was normal before employment, but had increased significantly at follow-up compared to technicians who had not developed LAA. Six of the nine LAA subjects had a more than threefold increase in bronchial responsiveness, and three of these reported chest symptoms. Spirometric values were not different between the groups prior to exposure or at follow-up, and had no prognostic value. However, a pre-employment level of total IgE > 100 kU.L-1 predicted the development of LAA (relative risk 2.8). Thus, early LAA was associated with increased bronchial responsiveness in most subjects. In contrast to total IgE, the level of pre-employment bronchial responsiveness or lung function did not influence the magnitude of change in responsiveness, nor predict sensitization.

Prospective study of laboratory-animal allergy: factors predisposing to sensitization and development of allergic symptoms.

In a prospective study of laboratory technicians, selected indicators of allergy and atopy were studied in an attempt to determine predictors of laboratory-animal allergy (LAA). Laboratory technicians underwent spirometry, methacholine provocation tests, and blood sampling, and responded to a questionnaire during training and after 2 years' work. Among 38 laboratory-animal-exposed subjects, total IgE before exposure gave the best correlation (P < 0.01; Mann-Whitney U-test) to reported symptoms caused by laboratory animals (n = 8) at follow-up. The prevalence of atopy and allergic symptoms had increased in exposed technicians at follow-up, but this was also found among unexposed matched referents (n = 36 pairs). One subject in the exposed group reported asthma before exposure, compared with seven at follow-up (P < 0.05; Fisher's exact test). However, the prevalence of asthma had increased from two to six (not significant) also among unexposed technicians. There were no significant differences between the groups in any measured variable at follow-up. Among 43 subjects who later worked with laboratory animals, 21% had a positive skin prick test for common allergens, as compared with 37% among 112 without animal exposure (P = 0.06; chi2 test), suggesting selection for laboratory animal work.

Changes in lung function of granite crushers exposed to moderately high silica concentrations: a 12 year follow up.

45 granite crushers and 45 age and smoking matched referents underwent pulmonary function tests in 1976 and 1988. On average, the granite crushers at follow up had worked for 22 years, were 52 (range 36-78) years old, and had inhaled a cumulated amount of 7 mg of silica in the respirable dust fraction. Between 1976 and 1988 the average concentration of respirable quartz in air was 0.16 mg/m3 (threshold limit value (TLV) = 0.10 mg/m3). In 1988 the granite crushers had somewhat lower forced expiratory flows (forced expiratory volume in one second/vital capacity (FEV1/VC) -4.5% and forced midexpiratory flow FEF50 -15%) compared with the referents and a more uneven ventilation distribution (17% higher slope of phase III in the nitrogen single breath curve). Five smoking granite crushers, but none of the referents, had an FEV1 < 80% of the predicted. During the 12 year interval the granite crushers had--compared with the matched referents--a greater decrease in FEV1 (-4.6%), FEV1/VC (-5.4%), maximal expiratory flow, (-8%) and FEF50 (-14%), and a larger increase in phase III and static compliance (p < 0.02 in all variables). The functional changes suggest the presence of airways obstruction and increased compliance of the lungs. Exposure to silica at concentrations of about twice the present TLV was thus associated with airways obstruction and loss of elastic recoil rather than fibrosis and a restrictive function loss as seen in silicosis. The changes were on average small, but in some tobacco smokers more pronounced changes were found.

Importance of the time interval between FEV1 measurements in a methacholine provocation test.

We examined the hypothesis that a forced expiratory volume in one second (FEV1) manoeuvre (and the preceding deep inhalation) before inhalation of methacholine might influence FEV1 measured after methacholine, if the time between measurements was short. Six to nine healthy subjects inhaled a single dose of methacholine, known to cause about 20% decrease in FEV1, on different days in different test protocols. If an FEV1 manoeuvre was performed immediately before methacholine, the first FEV1 measured 3 min after provocation was higher (77% of basal FEV1) than if a pre-methacholine FEV1 manoeuvre was not performed (64%). This effect of a pre-methacholine FEV1 manoeuvre was also demonstrated at 2, 4 and 6, but not at 10 min after the start of methacholine inhalation. If an FEV1 manoeuvre was not performed before methacholine, the second and subsequent FEV1 measured in constricted airways was higher than the first, and of similar magnitude to the first FEV1 in tests where a pre-challenge FEV1 manoeuvre was performed. In another trial, 10 healthy subjects performed two stepwise methacholine tests, with either 6 or 3 min between dose steps. The percentage decrease in FEV1 per mg of inhaled methacholine decreased from 2.6 (1.9-5.2) to 1.7 (0.8-2.3) (median, interquartile-range) when the time interval was shortened. The results suggest that the deep inhalation associated with the FEV1 manoeuvre decreases the bronchial tone in airways constricted by methacholine for up to 6 min, possibly due to yielding of cross-links in airway smooth muscles.