Menstrual cycle variation of retroperitoneal lymphangioleiomyomas in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare disease affecting women, classically involving the lungs. However, extrapulmonary manifestations also occur, including renal angiomyolipomas, retroperitoneal lymphangioleiomyomas and extrathoracic lymphadenopathy. The lung disease is hormone-responsive, but no information exists regarding sex hormone responsiveness of abdominal LAM. Here, we report two women with LAM whose abdominal lymphangioleiomyomas increased in size with hormonal changes of the menstrual cycle. This is the first description of abdominal lymphangioleiomyomas exhibiting hormone responsiveness in LAM. We describe these cases and summarize the literature on abdominal LAM. Menstrual cycle variation should be taken into account when assessing response to therapy, both clinically and in research studies.

Chest pain in asbestos and silica-exposed workers.

BACKGROUND: Chest pain may be the first symptom of developing respiratory malignancy, particularly in subjects with asbestos exposure, yet little information exists on this topic. AIMS: To investigate chest pain in a cohort of subjects exposed to asbestos and silica dust applying for compensation. METHODS: Cross-sectional study using a standardized questionnaire. Data collection included: smoking history, Medical Research Council scales of exercise capacity and respiratory symptoms. RESULTS: We studied 621 subjects. Six disease groups were categorized: asbestosis (n = 27), diffuse pleural thickening (DPT) (132), asbestosis and DPT (14), silicosis (26), pleural plaques only (160) and healthy subjects with a history of dust exposure (256). Crude prevalence rates of chest pain were high, with chest pain approximately twice as common in subjects with asbestos-related disorders and silicosis as in healthy subjects, with an overall frequency of ~40%. However, when other variables were taken into account in a multivariate analysis the differences between groups disappeared. The factor most significantly related to chest pain was age. CONCLUSIONS: Chest pain is apparently common in subjects with asbestos-related disorders and silicosis, but after adjustment for other variables, no increased prevalence was apparent in subjects with pleural disorders. More sophisticated questionnaires and dedicated imaging are required to elucidate this further.

Lupin allergy: a hidden killer at home, a menace at work; occupational disease due to lupin allergy.

The products of the flowering plant, lupin, are increasingly used as a human food product, particularly in baking. Occupational sensitization to lupin with occupational rhinitis, conjunctivitis and asthma was first described in 2001, and confirmed in a larger cross-sectional study in a food processing company in 2006. Sensitization by inhalation may result in occupational asthma, work-exacerbated asthma, occupational rhinitis and conjunctivitis. The incidence of occupational sensitization may be as high as 29%. The relationship with exposure intensity is as yet unclear, and requires further clarification. Although there is little information from long-term studies, these diseases are likely to improve after cessation of exposure. Cross-sensitization to other legumes, particularly peanuts, has been shown by skin prick testing, with potential for serious anaphylactic reactions. This review summarizes the available literature on occupational sensitization to lupin products. It is one of two reviews, one covering the problem of lupin allergy in the home, while the present article deals with lupin sensitization in the workplace. Increased awareness is needed of this occupational hazard to avoid future cases of occupational disease and their accompanying morbidity and potential mortality.

Surveillance of Australian workplace Based Respiratory Events (SABRE) in New South Wales.

BACKGROUND: The Surveillance of Australian workplace Based Respiratory Events (SABRE) New South Wales (NSW) scheme is a voluntary notification scheme established to determine the incidence of occupational lung diseases in NSW Australia. AIMS: Data presented in this paper summarize the last 7 years of reporting to SABRE (June 2001 to December 2008). METHODS: Every 2 months, participating occupational physicians, respiratory physicians and general practitioners (accredited by the NSW WorkCover Authority) reported new cases of occupational lung disease seen in their practices. Data collected include gender, age, causal agent and the occupations and industries believed responsible. Estimated incidence was calculated for each disease. RESULTS: Three thousand six hundred and fifty-four cases were notified to the scheme, consisting of 3856 diagnoses. Most of the cases were males (76%). Pleural plaques [1218 (28%)] were the most frequently reported condition, followed by mesothelioma [919 (24%)]. Silicosis [90 (2%)] and occupational asthma [OA; 89 (2%)] were the most frequently reported non-asbestos-related diseases. Estimated rates for mesothelioma, diffuse pleural thickening (DPT) and OA were 83, 83 and 5 cases per million employed males per year, respectively. Trades such as carpenters and electricians associated with the building industry, electricity supply and asbestos product manufacture were the most common occupations and industries reported. CONCLUSIONS: Asbestos-related diseases are the most frequently reported conditions to SABRE NSW. The very low incidence of OA for NSW most likely reflects under-diagnosis as well as under-reporting. Occupational lung disease is still occurring in NSW despite current preventative strategies. The SABRE scheme currently provides the only available information in this area.

L-arginine reverses cigarette-induced reduction of fractional exhaled nitric oxide in asthmatic smokers.

INTRODUCTION: Complex mechanisms regulate nitric oxide (NO) synthesis. Cigarette smoking decreases fractional exhaled NO (FE(NO)), while asthmatic inflammation increases FE(NO). To assess whether the smoking-induced decrease in FE(NO) levels was reversible, asthmatic and non-asthmatic smokers inhaled the NO synthase (NOS) substrate, L-arginine. Aminoguanidine, a relatively selective Type II NOS inhibitor, was used also to assess the role of NOS subtypes in these changes of FE(NO). METHODS: The study was a single-blinded, placebo-controlled, cross-over design in two parts. Part I: smoking asthmatic and non-asthmatic smoking subjects smoked one cigarette and then inhaled nebulised L-arginine or L-alanine (control). Spirometry, FE(NO), nasal NO (FN(NO)), FE(CO), were measured for 4 h. Part II: subjects inhaled nebulised aminoguanidine prior to an identical protocol as in Part I. Change in FE(NO) was assessed as area under the curve (AUC). RESULTS: Part I: In asthmatic smokers, cigarette smoking followed by L-arginine caused a significant median increase in AUC of 29.2(17)% FE(NO) change/hour (p = 0.04), which did not occur in non-asthmatic smokers (baseline FE(NO) 12.7(7.1-18) vs. 6.7(4-9.2) ppb, respectively). Part II: Aminoguanidine prior to smoking caused a significant fall in FE(NO) in both asthmatic and non-asthmatic smokers. L-arginine showed significant reversal of this effect in both asthmatic and non-asthmatic subjects. CONCLUSIONS: In asthmatic smokers, L-arginine increases FE(NO) after cigarette smoking but not in non-asthmatic smokers. The decrease in FE(NO) after aminoguanidine and subsequent partial reversal by L-arginine in both groups, suggests that Type II NOS contributes to the FE(NO) in both.

An electronic nose in the discrimination of breath from smokers and non-smokers: a model for toxin exposure.

Exhaled breath contains hundreds of volatile organic compounds (VOCs) that may be used as non-invasive markers of lung disease. Electronic noses (e-noses) can analyse VOCs by composite nanosensor arrays with learning algorithms. This study investigated the use of an e-nose (Cyranose C320) to distinguish the breath of smokers from that of non-smokers. Smoking and non-smoking subjects exhaled from total lung capacity into a 2 L Tedlar bag and these samples were introduced offline to the e-nose in a random order. Two classes of breath, 'smoker' and 'non-smoker', were established and this model was then cross-validated. Principal component analysis then identified the maximal point of difference between classes. Smellprints of breath from smokers were separated from those of non-smokers (cross-validation value, 95%; Mahalanobis distance, 3.96). Subsequently, 15 smokers (mean age 37.9 ± 4.78 years, FEV(1) 3.15 ± 0.21 L), and 24 non-smokers (add mean age and FEV1 as for smokers) were sampled to revalidate the model. The e-nose correctly identified the smoking status in 37 of the 39 subjects. This demonstrates that the e-nose is simple to use in clinical practice and can differentiate the breath of smokers from that of non-smokers. It may prove to be a useful, non-invasive tool for further breath assessment of exposure to other inhaled noxious substances as well as disease monitoring.

Pulmonary necrobiotic nodules: a rare extraintestinal manifestation of Crohn's disease.

The present article reports the case of a 22-yr-old female with new onset Crohn's colitis, anterior uveitis and multiple pulmonary nodules which, on histological examination, were necrobiotic nodules. This is a rare but recognised pulmonary extraintestinal manifestation of Crohn's disease and only the fourth reported case. The present case report is followed by a brief review of the relevant literature.

Biomarkers in pulmonary hypertension.

There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment. The present article details the more important biomarkers, their potential applications and the evidence supporting their use.

AMP challenge induces a decrease in FE(NO) in asthmatic subjects modulated by nedocromil.

BACKGROUND: Allergen challenge results in an immediate reduction in exhaled nitric oxide (FE(NO)) followed by a long-term increase. To study mast cell activation in relation to nitric oxide (NO), the study investigated the effect of inhaled adenosine monophosphate (AMP) as a mast cell activator and mast cell stabilizer - nedocromil sodium - on FE(NO). The NO synthase (NOS) iso-enzyme involved was studied by the NOS inhibitor aminoguanidine. MATERIALS AND METHODS: A double-blind, placebo-controlled, cross-over study was performed in two parts. Part I: eight atopic asthmatic subjects inhaled nedocromil or placebo before the AMP challenge. Spirometry and FE(NO) were measured at intervals over a 24-h period. Part II: seven subjects inhaled aminoguanidine before an identical protocol was used, as in Part I. RESULTS: Part I: AMP challenge caused a significant decrease from baseline FE(NO)[placebo, 28.9 (20.3-37.4)%, P < 0.002 and nedocromil, 20.9 (8.2-33.6)%, P < 0.01]. Nedocromil gave partial protection against this decrease in FE(NO). The time-FE(NO) curve (AUC(0-24)) differed significantly between nedocromil and placebo: 2.7% (-3.6 to -9) vs. -6.6% (-12 to -1.3) FE(NO) changes h(-1), P < 0.002, respectively. Nedocromil protected against AMP-induced bronchoconstriction (AMP PC(20)) [nedocromil 182 (72.5-291) mg mL(-1) vs. placebo 21.7 (10.7-33) mg mL(-1), P < 0.002]. Part II: nebulized aminoguanidine resulted in a significant reduction in FE(NO) from baseline and was greater than after AMP alone (P = 0.006). Nedocromil increased AMP PC(20), but no longer protected against the late decrease in FE(NO). CONCLUSIONS: The AMP challenge caused a reduction in FE(NO) as a result of prior treatment with nedocromil. Aminoguanidine abolished the nedocromil-induced protection on the late reduction in FE(NO), but not on AMP PC(20). Inducible NOS was implicated in the late FE(NO) decrease after the AMP challenge.

Cold blast furnace syndrome: a new source of toxic inhalation by nitrogen oxides.

AIM: To describe a new toxic inhalation syndrome in blast furnace workers. METHODS: Fourteen workers developed acute respiratory symptoms shortly after exposure to "air blast" from blast furnace tuyeres. These included chest tightness, dyspnoea, rigors, and diaphoresis. Chest radiographs showed pulmonary infiltrates, and lung function a restrictive abnormality. This report includes a description of clinical features of the affected workers and elucidation of the probable cause of the outbreak. RESULTS: Clinical features and occupational hygiene measurements suggested the most likely cause was inhalation of nitrogen oxides at high pressure and temperature. While the task could not be eliminated, engineering controls were implemented to control the hazard. No further cases have occurred. CONCLUSIONS: "Cold blast furnace syndrome" represents a previously undescribed hazard of blast furnace work, probably due to inhalation of nitrogen oxides. It should be considered in the differential diagnosis of acute toxic inhalational injuries in blast furnace workers.

Laughter-associated asthma.

This study was conducted to assess the prevalence of laughter-induced asthma, and to study any associations with asthma-related triggers and measures of disease activity, using a questionnaire-based survey of asthma subjects in both the community and on presentation to hospital. A total of 105 subjects participated, and 44 (41.9%) reported laughter-associated asthma. Exercise and laughter were strongly associated as triggers (p < 0.006), as well as molds and grass pollen (p = 0.03). It seems to be associated with poor asthma control as well, since hospital admissions are also more frequent in this group (p = 0.043). Laughter-induced asthma is strongly associated with exercise as a trigger; the mechanism remains uncertain, but better understanding of this problem may assist in controlling difficult asthma.

Health and stress in Australian interns.

Over a 3-year period, interns completed questionnaires on self-reported health and stress during their orientation week at the beginning of the year, during mid year, and at the end of the first year. Interns experienced increased levels of stress and ill health in the middle of the year as compared with the start and end of the year (chi2=11.9, P=0.003 and chi2=20.4, P<0.001, respectively). Despite workplace reform for junior doctors, this study suggests that interns still feel overburdened with work expectations and this is having a negative effect on their health.

Particulate masks and non-powdered gloves reduce latex allergen inhaled by healthcare workers.

BACKGROUND: Although allergy to latex is a well-characterized phenomenon, some hospitals continue to provide staff with powdered latex gloves as an option to low- or non-powdered gloves. OBJECTIVE: We aimed to measure the extent to which inhalation of latex particles could be reduced by the use of protective masks or by replacing powdered latex gloves with non-powdered latex gloves. METHODS: Twenty healthcare workers in a hospital setting wore nasal air samplers (NAS) and Institute of Occupational Medicine (IOM) samplers for four 20-min periods. Subjects wore powdered gloves, non-powdered gloves and no gloves during three sampling periods, and in the fourth, subjects applied an aerosol barrier face-mask or a particulate face-mask (N95) while wearing powdered gloves. All samples were stained for particles bearing Hev b 5 allergen by the Halogen assay. RESULTS: All subjects inhaled Hev b 5 bearing particles in all sampling periods. IOM samplers collected particles at 70% of the rate of NAS. The number of particles inhaled while wearing powdered gloves was 23.8-fold higher than when not wearing gloves and 9.7-fold higher than when wearing non-powdered latex gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce the number of particles inhaled (P = 0.108), while use of particulate masks significantly reduced the number of particles inhaled by 17.4-fold (P = 0.003). CONCLUSIONS: Use of non-powdered gloves is the most effective method of reducing occupational aeroallergen exposure to latex arising from gloves. However, secondary protection using particulate masks is a valid alternative, and may be helpful for preventing respiratory sensitization.

Caffeine decreases exhaled nitric oxide.

BACKGROUND: Caffeine is known to inhibit phosphodiesterases, to mobilise intracellular calcium, and to act as an antagonist at adenosine receptors, all of which can potentially alter nitric oxide (NO) production. It was therefore hypothesised that caffeine may alter exhaled NO (eNO) levels. METHODS: In a randomised, single blind, crossover manner, 12 normal subjects consumed either (1) coffee and a placebo capsule, (2) decaffeinated coffee and a capsule of 200 mg caffeine, or (3) decaffeinated coffee and a placebo capsule. Serum caffeine levels were measured at baseline and 1 hour later. Exhaled NO levels were also measured at baseline and each hour for 4 hours. RESULTS: A significant percentage fall in mean (SE) eNO from baseline was seen 1 hour after either caffeinated coffee or a caffeine capsule when compared with placebo (13.5 (4.0)%, p=0.009 and 19.0 (3.8)%, p=0.001, respectively). CONCLUSION: Caffeine causes a significant decrease in eNO which will need to be considered when designing trials to measure eNO levels. The mechanism may be via adenosine receptor antagonism or by altering levels of cGMP.

Passive smoke inhalation decreases exhaled nitric oxide in normal subjects.

Environmental tobacco smoke (ETS) exposure is one of the commonest pollutants in modern society. Despite documented clinical adverse effects of ETS on the lungs, objective methods of assessing airway damage have been lacking. Exhaled nitric oxide (eNO) is a rapid, sensitive method of assessing airway inflammation, and could be useful in this regard. Active smoking decreases eNO in normal subjects and eNO levels are low in habitual smokers, but the effect of ETS exposure on eNO has not previously been examined. In a single-blinded, placebo-controlled cross-over study, we examined the effect of ETS, sham and active smoke inhalation on eNO in non-smoking normal volunteers. Subjects were exposed to smoke over a period of 1 hour in a separately ventilated chamber, and eNO was measured at baseline, 15, 30, 45 and 60 minutes. With sham inhalation (n = 15), eNO levels did not change significantly from baseline, although a small decrease occurred. ETS exposure (n = 15) resulted in a rapid fall in eNO from mean (SE) 134 (29) ppb to 102 (22) ppb, or by 23.6% (p < 0.05), and remained low for 60 minutes. With active smoking (n = 7), levels fell acutely from baseline within the same time interval (71 [16] to 49 [11] ppb, or by 30.3%), and remained low. These changes were significant compared with sham exposure for both ETS (p < 0.05) and active smoke inhalation (p <.01). This suggests that eNO can be used for the investigation of the mechanisms of cigarette-induced lung damage in the experimental setting, and may potentially be useful also for environmental assessment of ETS effects.