Spirometry or Body Plethysmography for the Assessment of Bronchial Hyperresponsiveness?

Methacholine testing is one of the standard tools for the diagnosis of mild asthma, but there is little information about optimal outcome measures. In this study a total of 395 college students were tested by the ATS dosimeter protocol for methacholine testing, with minor modification. Body plethysmography and spirometry were measured after each inhalation step. The end-of-test-criteria were (i) decrease in forced expiratory volume in 1 s (FEV1) of ≥ 20 % and (ii) doubling of specific airway resistance and its increase to ≥ 2.0 kPa∙s. The results were expressed by receiver operating characteristic (ROC) plots using questionnaire answers as a reference. The areas under the ROC curves were iteratively calculated for a wide range of thresholds for both measures. We found that ROC plots showed maximal sensitivities of about 0.5-0.6 for FEV1 and about 0.7 for specific airway conductance (sGt), with similar specificities of about 0.7-0.8 taking questions with the known high specificity as references. Accordingly, larger maximal areas under the ROC curve were observed for body plethysmography, but the differences were small. A decrease in FEV1 of about 15 % and a decrease of sGt of about 60 % showed the largest areas under the ROC curves. In conclusion, body plethysmography yielded better sensitivity than spirometry, with similar specificity. However, replacing the common spirometric criterium for a positive test (20 % decrease in FEV1 from baseline) by the optimal body plethysmographic criterium would result in an increase of false positive tests from about 4 to 8 % in healthy young adults.

Allergic asthma after flour inhalation in subjects without occupational exposure to flours: an experimental pilot study.

OBJECTIVE: Cross-reactivity between grass pollen and grain flour allergens is well known, but their significance in apprentice bakers with primary sensitization to grass pollen is not known. METHODS: Twenty-five subjects with mild asthma (most of them with hay fever), but without prior occupational flour exposure, underwent standardized experimental inhalation challenges with placebo and wheat and rye flours in randomized order on three consecutive days. Sensitization to flours and environmental allergens was assessed by skin prick tests and specific IgE antibodies in sera. IgE inhibition experiments were performed with wheat and rye flours as solid phases, and grass and tree pollen as inhibitors. RESULTS: Five subjects experienced a positive reaction after flour inhalation (responders), whereas 20 subjects did not show such a reaction (non-responders). All responders showed sensitizations to flours, whereas only 25% of the non-responders demonstrated the same sensitization. Specific IgE concentrations to flours, but also to grass and tree pollen, were higher in responders. Inhibition experiments demonstrated cross-reactivity between flours and grass or tree pollen, with higher inhibition rates in responders. CONCLUSIONS: Subjects with pronounced sensitizations to grass or tree pollen, but without prior occupational exposure to flours, may experience both sensitization and allergic asthmatic reactions to flours due to cross-reactive grass and tree pollen allergens.

The German experience 10 years after the latex allergy epidemic: need for further preventive measures in healthcare employees with latex allergy.

OBJECTIVES: Powdered latex gloves or latex gloves with high allergen content are forbidden in Germany since 1998. It was the aim of this study to test the hypothesis that nationwide preventive measures enable health care workers with latex allergy to work without health risks about 10 years afterwards. METHODS: Ninety-one health care workers who had been reported to the accident insurance between 1996 and 2004 for occupational latex allergy were examined in 2007. The survey included a questionnaire, a physical examination, spirometry, methacholine testing, skin prick testing and serum IgE measurements to latex and environmental allergens. RESULTS: Recent work-related possibly allergic symptoms were reported by 32 subjects (35%), among them 18 subjects (20%) with symptoms of the eyes, nose or airways. Current sensitization to latex was detected in 61 subjects (67%), and 60 subjects (66%) were atopic. Eleven subjects (12%) showed mild airway obstruction, and 27 subjects (30%) were considered hyperresponsive to methacholine. Whereas overall recent symptoms of the eyes, nose or airways were associated with current latex sensitization (OR 4.5; 95% CI 1.3-16.2), this was not the case for objective outcome parameters (spirometry, bronchial hyperresponsiveness). CONCLUSIONS: Although most subjects had only mild disease, ongoing work-related symptoms of the eyes, nose or airways in a substantial number of subjects with latex allergy suggest the need for further secondary preventive measures in German healthcare.

Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1).

BACKGROUND: Skin prick testing (SPT) is the basic method for diagnosing IgE-mediated allergies. However, skin reactivity is related to the quality of allergen extracts, which are often poorly defined for occupational allergens. OBJECTIVE: To compare wheat and rye flour SPT solutions from different producers. MATERIALS AND METHODS: Standardized SPTs were performed in seven allergy centres with wheat and rye flour solutions from four producers in 125 symptomatic bakers. Optimal cut-off levels for weal sizes were assessed with the Youden Index. Comparisons between SPT results of different solutions were made with flour-specific IgE (sIgE) as the gold standard. Sensitivities, specificities, positive and negative predictive values, and test efficiencies were calculated and compared with McNemar and chi(2)-tests. The influence of the choice of the gold standard (sIgE or challenge) test was examined for 95 subjects. Additionally, SPT solutions were analysed for protein and antigen content. RESULTS: The optimal cut-off level for all SPT solutions was a weal size of >or=1.5 mm. While differences between wheat and rye flours were small, differences between producers were important. Variability of sensitivities (0.31-0.96), negative predictive values (0.42-0.91), and test efficiencies (0.54-0.90) were higher than variations of specificities (0.74-1.00) and positive predictive values (0.88-1.00). Similar results were obtained when using challenge test results as the gold standard. Variability could be explained by the different antigen contents of the SPT solutions. CONCLUSION: There is a wide variability of SPT solutions for wheat and rye flour from different producers, mainly with respect to sensitivities, negative predictive values, and test efficiencies. Improvement and standardization of SPT solutions used for the diagnosis of baker's asthma are highly recommended.

Consort hypersensitivity pneumonitis.

To date, there is little information in the literature that hypersensitivity pneumonitis due to birds may occur without direct contact to birds. A 62-yr-old pensioner developed mild flu-like symptoms, fatigue and polyuria several hours after each meeting with his new female partner, either in hotels or his apartment. After divorcing from her ex-husband, who was a canary fancier, the female had moved into a bungalow approximately 6 months earlier. When the couple met for the first time at the bungalow, the patient's symptoms worsened and he developed shortness of breath. The patient had never entered the bird house or the married couple's house. Hypersensitivity pneumonitis was demonstrated by chest radiography, computed tomography, a restrictive ventilatory defect, decreased diffusion capacity and hypoxaemia after physical exercise. Sensitisation to canaries was shown by immunoassays. Canary antigens were detected by a polyclonal immunoassay at different locations of the married couple's house and the female's bungalow, where no birds had ever been kept. In conclusion, hypersensitivity pneumonitis should be recognised as a further consort disease, i.e. a disease that can be transmitted by partners.

Occupational hypersensitivity pneumonitis due to molds in an onion and potato sorter.

A 42-year-old female non-smoking onion and potato sorter developed work-related shortness of breath, cough, fatigue and flu-like symptoms. The diagnosis of hypersensitivity pneumonitis was based on patchy infiltrates in both lungs on high resolution computed tomography and lymphocytosis of 71% in a bronchoalveolar lavage sample with a CD4/CD8 ratio of 0.4. Exposure cessation and initial corticosteroid therapy resulted in complete recovery. IgG antibodies to Penicillium species and Fusarium solani cultivated from samples from the patient's workplace were detected in the patient's serum and cross-reactivity was demonstrated within Penicillium species, but also between Penicillium species and Aspergillus fumigatus. We conclude that occupational hypersensitivity pneumonitis due to molds may develop in onion and potato sorters.

Occupational immunoglobulin E-mediated asthma due to Penicillium camemberti in a dry-sausage packer.

A 62-year-old female sausage packer reported progressive work-related asthma, rhinitis and contact urticaria after contact to dry sausages refined by moulds. Whereas skin prick tests with commercial mould extracts were negative, the patient showed weak skin sensitization to a cultivated mould sample from a dry sausage. Specific immunoglobulin E antibodies to various moulds were demonstrated by ImmunoCAP and antibodies to the cultivated mould sample were demonstrated by enzyme allergosorbent test. The mould was identified by pheno- and genotyping as Penicillium camemberti. Five atopic controls did not show sensitization with the same tests. Crossreactivity of P. camemberti and Penicillium notatum was shown by enzyme allergosorbent inhibition tests. Although no challenge tests were considered due to the patient's airway obstruction, a diagnosis of allergic occupational asthma was made. We conclude that immunoglobulin E-mediated allergic occupational asthma due to moulds may occur in dry sausage packers.

The interobserver-validated relevance of intervertebral spacer materials in MRI artifacting.

Intervertebral spacers for anterior spine fusion are made of different materials, such as titanium, carbon or cobalt-chrome, which can affect the post-fusion MRI scans. Implant-related susceptibility artifacts can decrease the quality of MRI scans, thwarting proper evaluation. This cadaver study aimed to demonstrate the extent that implant-related MRI artifacting affects the post-fusion evaluation of intervertebral spacers. In a cadaveric porcine spine, we evaluated the post-implantation MRI scans of three intervertebral spacers that differed in shape, material, surface qualities and implantation technique. A spacer made of human cortical bone was used as a control. The median sagittal MRI slice was divided into 12 regions of interest (ROI). No significant differences were found on 15 different MRI sequences read independently by an interobserver-validated team of specialists (P>0.05). Artifact-affected image quality was rated on a score of 0-1-2. A maximum score of 24 points (100%) was possible. Turbo spin echo sequences produced the best scores for all spacers and the control. Only the control achieved a score of 100%. The carbon, titanium and cobalt-chrome spacers scored 83.3, 62.5 and 50%, respectively. Our scoring system allowed us to create an implant-related ranking of MRI scan quality in reference to the control that was independent of artifact dimensions. The carbon spacer had the lowest percentage of susceptibility artifacts. Even with turbo spin echo sequences, the susceptibility artifacts produced by the metallic spacers showed a high degree of variability. Despite optimum sequencing, implant design and material are relevant factors in MRI artifacting.

Identification of an obeche (Triplochiton scleroxylon) wood allergen as a class I chitinase.

BACKGROUND: Wood dust is known to cause allergic occupational asthma and obeche (Triplochiton scleroxylon) is a prominent exponent in this field. However, the knowledge about wood allergens is still limited. The aim of this study was to identify and characterize obeche wood allergens. METHODS: Obeche extracts were prepared from freshly ground in comparison to 7 years stored wood dust and investigated by Sodium dodecyl sulfate-polyacrylamid gel electrophoresis, enzyme-linked allergosorbent test and immunoglobulin (Ig)E-immunoblot. Allergens were detected by specific IgE of seven obeche allergic patients' sera and protein analysis was performed by mass spectrometry. Cross-reactivity was demonstrated by ImmunoCAP-inhibition with sera of seven obeche and four latex-allergic patients. RESULTS: Obeche extracts showed different protein pattern and IgE-binding capacities depend on the age of the wood dust. A 38 kDa protein was identified as major obeche wood allergen, detected by six of seven (85%) obeche allergic patients' sera and was entitled as Trip s 1. Trip s 1 is homologous to plant class I chitinases and exhibited enzyme activity demonstrated by chitinolysis. Co-recognition or cross-reactivity of Trip s 1 according to structural similarity was seen in sera of latex allergic patients. IgE inhibition studies with obeche as solid phase and Trip s 1 and latex hevein as inhibitor demonstrated that Trip s 1 was a more effective inhibitor in obeche as well as in latex allergic patients' sera. CONCLUSIONS: Trip s 1 is a new obeche wood allergen of the plant class I chitinase family. This finding may explain the dominant role of obeche in sensitization against wood dust.

Comparison of IgE antibody concentrations to pyromellitic dianhydride-modified laminin and human serum albumin in sera of exposed workers with respiratory complaints.

BACKGROUND: Acid anhydrides are used in a variety of industrial branches because of their highly reactive anhydride groups. Adverse effects of anhydride exposure include toxic/irritative effects as well as IgE- and IgG-mediated respiratory disorders. It was the aim of this study to examine the usefulness of conjugates of pyromellitic dianhydride (PMDA) and laminin, a respiratory tract protein, for the in vitro diagnosis of sensitization to PMDA. METHODS: Sera of PMDA-exposed workers (n = 9) and nonexposed controls (n = 8) were tested with an enzyme allergosorbent test (EAST). Human laminin and human serum albumin (HSA) were derivatized with PMDA and used as solid-phase in a commercial assay. RESULTS: Seven out of 9 exposed workers revealed elevated IgE antibody concentrations (>0.35 kU/l) against laminin-PMDA whereas 5 of 9 subjects had elevated IgE antibody concentrations to HSA-PMDA. All 9 workers had elevated IgE antibody concentrations in at least one of the two tests. Of the 4 workers who complained of shortness of breath, 3 were positive for laminin-PMDA and 2 for HSA-PMDA. All of the nonexposed subjects were negative (<0.35 kU/l) for laminin-PMDA. CONCLUSION: PMDA-modified laminin could provide an additional diagnostic tool for the detection of sensitization to PMDA.

Health hazards due to the inhalation of amorphous silica.

Occupational exposure to crystalline silica dust is associated with an increased risk for pulmonary diseases such as silicosis, tuberculosis, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and lung cancer. This review summarizes the current knowledge about the health effects of amorphous (non-crystalline) forms of silica. The major problem in the assessment of health effects of amorphous silica is its contamination with crystalline silica. This applies particularly to well-documented pneumoconiosis among diatomaceous earth workers. Intentionally manufactured synthetic amorphous silicas are without contamination of crystalline silica. These synthetic forms may be classified as (1) wet process silica, (2) pyrogenic ("thermal" or "fumed") silica, and (3) chemically or physically modified silica. According to the different physicochemical properties, the major classes of synthetic amorphous silica are used in a variety of products, e.g. as fillers in the rubber industry, in tyre compounds, as free-flow and anti-caking agents in powder materials, and as liquid carriers, particularly in the manufacture of animal feed and agrochemicals; other uses are found in toothpaste additives, paints, silicon rubber, insulation material, liquid systems in coatings, adhesives, printing inks, plastisol car undercoats, and cosmetics. Animal inhalation studies with intentionally manufactured synthetic amorphous silica showed at least partially reversible inflammation, granuloma formation and emphysema, but no progressive fibrosis of the lungs. Epidemiological studies do not support the hypothesis that amorphous silicas have any relevant potential to induce fibrosis in workers with high occupational exposure to these substances, although one study disclosed four cases with silicosis among subjects exposed to apparently non-contaminated amorphous silica. Since the data have been limited, a risk of chronic bronchitis, COPD or emphysema cannot be excluded. There is no study that allows the classification of amorphous silica with regard to its carcinogenicity in humans. Further work is necessary in order to define the effects of amorphous silica on morbidity and mortality of workers with exposure to these substances.

Equivalent sensation curves of simultaneous lateral and vertical sinusoidal whole-body vibration.

BACKGROUND: To evaluate the effects of whole body vibration on discomfort, the sensitivity to different frequencies as well as to different vibration axes must be regarded. This experimental study investigates the significance of lateral relative to vertical motions in the sensation of dual axis sinusoidal vibrations in sitting posture. The results are discussed in the context of the evaluation procedure proposed in the international standard ISO 2631 (13). METHODS: The experiments, in which 31 volunteers (16 female, 15 male, 19 51 yr) participated, used the method of adjustment. The subjects compared a single axis reference motion (aw = 1.25 ms(-2) rms) with a dual axis test motion of the same frequency. The magnitude of the test signal's component along the reference axis was kept constant at a fractional level of the reference magnitude (10, 25, 50, 75 or 90%). The component perpendicular to the reference axis was adjusted by the subjects until the test signal was rated as being equally strong as the reference. Both vertical and lateral reference motions were applied. The frequencies used were 1.6, 3.15, 6.3 and 12.5 Hz. RESULTS: The shape of the resulting right-downwards bent equivalence curves was reasonably well fitted using the frequency weightings and evaluation procedure of ISO 2631. However, there were considerable quantitative discrepancies for frequencies above 1.6 Hz with an underestimation of the effects of lateral vibrations by a factor of 1.5-2. Therefore, it is concluded that lateral vibrations above 1.6 Hz need more weight in the evaluation of discomfort caused by multi-axis whole body vibrations.