Prevention of baker's asthma.

PURPOSE OF REVIEW: Baker's allergy and asthma continue to represent an important contributor of occupational asthma globally. This review identified recent studies related to the prevention of baker's allergy and asthma. RECENT FINDINGS: Studies with respect to regulatory exposure standards, workplace control measures aimed at reduction of flour dust exposures, surveillance programmes (exposure monitoring, medical surveillance) and workplace information, education and training programmes were identified. SUMMARY: Detailed knowledge on risk factors and detection methods to assess exposure and early identification of high-risk workers exist, but workplace control measures remain sub-optimal because they are rarely multifaceted. This is compounded by the lack of health-based exposure standards globally. Exposure level monitoring and medical surveillance are integral to assessing effectiveness of preventive strategies. Triage systems for optimizing the efficiency of medical surveillance programmes show promise, but need replication in different contexts. Future studies need to focus on evaluating the relevance and quantification of peak exposures in increasing risk; developing standardized respiratory questionnaires for medical surveillance; and further exploration of serial fractional exhaled nitric oxide (FeNO) measurements as an adjunct to allergic sensitization for the early identification of baker's asthma and assessing the long-term impact of interventions.

Hypersensitivity Pneumonitis Due to Metalworking Fluid Aerosols.

PURPOSE OF REVIEW: This review summarises the clinical knowledge of hypersensitivity pneumonitis in workers exposed to aerosols of metalworking fluid, reviewing published outbreaks and clinical cases. RECENT FINDINGS: Metalworking fluid exposure has become the commonest recognised cause of occupational hypersensitivity pneumonitis, having been rare before 2000. There are many possible agents in the metalworking fluid which may be the cause of disease including bacteria, mycobacteria, fungae, biocides, emulsifiers, reodorants and dissolved chrome and cobalt. Causes are likely to be different in different outbreaks. Mycobacteria growing in the metalworking fluid have generated immune responses in some workers, but their role in disease causation is not yet established. Many outbreaks have been identified in large workplaces using common sumps. It is not possible to prevent microbial contamination of metalworking fluids in use. Disease prevention should focus on stopping inhalation of aerosols, particularly by re-engineering to remove recirculation.

Revisión de la enfermedad del pulmón de granjero / Farmer's Lung Disease. A Review

La enfermedad del pulmón de granjero (EPG) es una forma de neumonitis por hipersensibilidad (NH) producida por la inhalación de microorganismos procedentes del heno o grano almacenado en condiciones de alta humedad en el ámbito laboral agrícola. Se trata de una enfermedad probablemente infradiagnosticada, sobre todo en el Norte de España, donde las condiciones climáticas son propicias para el desarrollo de la misma. Según estudios previos los antígenos más frecuentes suelen ser hongos y actinomicetos termofílicos. La epidemiología de la enfermedad no es del todo bien conocida, y se basa en estudios realizados por grupos centroeuropeos y asiáticos. La presentación clínica puede ser variada, diferenciándose las formas agudas (tras exposición a elevadas concentraciones del antígeno) y las crónicas (exposición a menores concentraciones del antígeno, pero más prolongada en el tiempo). En estos casos es esencial, en aquellos pacientes con clínica respiratoria durante la exposición laboral agrícola, demostrar una radiología y función pulmonar compatible, así como una sensibilización al antígeno, una linfocitosis en el lavado broncoalveolar en su caso y/o una anatomía patológica concordante. El tratamiento principal es la evitación antigénica, por lo que la educación de los pacientes en las medidas preventivas es fundamental. Por el momento, no existen estudios controlados que permitan evaluar el papel de tratamientos inmunosupresores en esta enfermedad. El tratamiento con corticosteroides solo ha demostrado acelerar la resolución de las formas agudas, pero no hay estudios que demuestren su efectividad a largo plazo, con el fin de evitar la progresión de la enfermedad ni disminuir su mortalidad

Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality

Hypersensitivity Pneumonitis.

Chronic exposure to a broad array of antigens after workers inhale aerosolized organic dust particles from mold, animal dander, bird droppings, and chemicals, especially pesticides or herbicides, increases risk for hypersensitivity pneumonitis. Several demographic characteristics of immigrant workers in farming, poultry processing, construction, and landscaping increase this worker population's risk.

Chemical determinants of occupational hypersensitivity pneumonitis.

BACKGROUND: Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA). AIMS: To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA. METHODS: Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorized according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure-activity relationship (QSAR) model. The chemicals in both sets were independently and 'blindly' analysed by an expert in mech anistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log K ow). RESULTS: Ten HP-causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA-causing chemicals (P < 0.01). Nine of 10 HP-causing chemicals were predicted to be protein cross-linkers compared with 24/92 controls (P < 0.001). The distributions of log K ow indicated higher values for the HP list (median 3.47) compared with controls (median 0.81) (P < 0.05). CONCLUSIONS: These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA.

Exposure to low doses of formaldehyde during pregnancy suppresses the development of allergic lung inflammation in offspring.

Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment.

Discovery of GW870086: a potent anti-inflammatory steroid with a unique pharmacological profile.

BACKGROUND AND PURPOSE: Glucocorticoids are highly effective therapies for a range of inflammatory diseases. Advances in the understanding of the diverse molecular mechanisms underpinning glucocorticoid action suggest that anti-inflammatory molecules with reduced side effect liabilities can be discovered. Here we set out to explore whether modification of the 17α position of the steroid nucleus could generate molecules with a unique pharmacological profile and to determine whether such molecules would retain anti-inflammatory activity. EXPERIMENTAL APPROACH: The pharmacological properties of GW870086 were compared with fluticasone propionate (FP) using a range of cellular and in vivo model systems, including extensive gene expression profiling. KEY RESULTS: GW870086 repressed inflammatory cytokine release from lung epithelial cells in a similar manner to FP but antagonized the effect of dexamethasone on MMTV-driven reporter gene transactivation. GW870086 had a strong effect on the expression of some glucocorticoid-regulated genes (such as PTGS2), while having minimal impact on the expression of other known target genes (such as SGK). GW870086 retained the ability to strengthen tight junctions in epithelial cell culture but, unlike FP, was unable to protect the culture from elastase-mediated damage. In murine models of irritant-induced contact dermatitis and ovalbumin-induced allergic inflammation, GW870086 showed comparable anti-inflammatory efficacy to FP. CONCLUSION AND IMPLICATIONS: GW870086 is a potent anti-inflammatory compound with a unique ability to regulate only a subset of those genes that are normally affected by classical glucocorticoids. It has the potential to become a new topical steroid with a different safety profile to existing therapies.

Inadequate access to diagnostic resources: a case of unrecognised hypersensitivity pneumonitis.

OBJECTIVE: Hypersensitivity pneumonitis (HP) often goes unrecognized because of its relatively low incidence in the general population and it is frequently misdiagnosed as a respiratory infection or idiopathic interstitial lung disease. METHODS: Through the analysis of a paradigmatic case of hypersensitivity pneumonitis, in which only symptomatic diagnosis and treatment were proposed, we argue that limiting the clinical process to generic diagnosis, without detection of the etiologic agent, makes it impossible to avoid exposure, hinders compensation and severely worsens the evolution of the disease. RESULTS: In 1981, a previously healthy, 28-year-old female clerk developed respiratory symptoms. She was diagnosed as suffering from extrinsic bronchial asthma and was treated with steroids and broncho-dilators. Neither immunologic tests nor any environmental pathogen research were proposed until 2008, when precipitins analysis showed positivity to Thermoactynomyces vulgaris, which had presumably contaminated the centralized air-conditioning system. CONCLUSIONS: The diagnosis of HP is unlikely to be missed if in all clinical settings, occupational or environmental causes are routinely considered in the differential diagnosis of any patient with a respiratory problem. This approach could provide a better clinical management of the disease and more effective programmes of primary prevention. Implicit rationing of healthcare resources by limiting diagnostic tests that are not readily accessible reduces patient autonomy and the benefits of medical care.

[Domestic hypersensitivity pneumonitis]. / Pneumopathies d'hypersensibilité domestiques. Alvéolites allergiques extrinsèques domestiques.

INTRODUCTION: Domestic hypersensitivity pneumonitis (HP) cases are relatively widespread, with an overall annual incidence of approximately 1/100,000 reported in a British study covering several million patients. All-causes mortality is three times higher within HP-affected patients than amongst the general population. STATE OF THE ART: Cases of HP are usually diagnosed as 'farmer's lung' (FL) and 'bird fancier's lung' (BFL) diseases, however we suggest that other domestic causes, such as humidifier lung, hot tub pneumonitis, feather duvet and domestic exposure to moulds may be more frequent than widely suggested. Usually, the diagnosis is established on the basis of characteristic clinical, functional, radiological and broncho-alveolar lavage findings or recurrence of respiratory symptoms after returning home. PERSPECTIVES: In the absence of a common cause (FL or BFL), physicians must have a high index of clinical suspicion and should consider an environmental antigen source. Detailed questioning of HP patients on their living conditions and, where appropriate, a home inspection conducted by an environmental health expert are necessary for identifying causative antigens. CONCLUSION: The cornerstone of therapy is antigen avoidance.

Alveolitis alérgica extrínseca: forma de presentación inicial como fiebre de origen desconocido / Extrinsic allergic alveolitis: an initial form of presentation as a fever of unknown origin

La alveolitis alérgica extrínseca se caracteriza por un proceso inflamatorio inmunológico con afectación pulmonar producida por inhalación de polvo orgánico. Se considera una enfermedad laboral y es una causa muy importante de incapacidad transitoria y permanente que se puede evitar. Ocasionalmente el diagnóstico no es sencillo, pero es importante realizarlo en los primeros estadios, cuando todavía es reversible la enfermedad (AU)

Extrinsic allergic alveolitis is characterised by an inflammatory immune process with pulmonary impairment caused by inhalation of organic dust. It is considered an occupational disease and is a very significant cause of temporary and permanent disability that can be prevented. The diagnosis is not often easy, but it is important to make it in the early stages, when the disease is still reversible (AU)

Implementation of a quantitative real-time PCR assay for the detection of Mycobacterium immunogenum in metalworking fluids.

The bacterium Mycobacterium immunogenum has been implicated in causing the lung condition hypersensitivity pneumonitis (HP) in factory workers exposed to colonized metalworking fluids (MWFs). M. immunogenum-specific, real-time quantitative PCR detection technique (MiRT-qPCR) was implemented on a large scale to 363 MWFs of varying types, originating from the United States and Europe, that had been in use for between 30 days and 1 year. In MWFs that contained between 10(3) and 10(9) culturable general heterotrophs mL(-1) the technique detected between 5 and 2 × 10(6) mL(-1) M. immunogenum cell equivalents (CE) in 12.2% (23 of 189) of U.S. samples and between 8 and 6 × 10(5) mL(-1) CE in 39.1% (68 of 174) of samples from Europe. In contrast, only three cultured presumptive mycobacterial isolates across all samples were confirmed as M. immunogenum. Implementation of the assay demonstrated its practicality and further emphasized the limitations of using cultivation alone. Interestingly, no M. immunogenum were detected in mineral oil-based Bio-Concept MWFs from the United States, while it was more commonly detected in used MWFs based on formaldehyde-releasing biocides than in MWFs free of formaldehyde-depot biocides.

Nontuberculous mycobacterial hypersensitivity pneumonitis related to a home shower: treatment and secondary prevention.

A 57-year-old physician with increasing dyspnoea and hypoxaemia had a high-resolution CT scan of the chest, which disclosed diffuse pulmonary ground glass opacities, more pronounced in the upper lobes with minimal mediastinal lymphadenopathy. Transbronchial biopsy of the right middle and lower lobes was performed, demonstrating varying degrees of well circumscribed organising granulomatous pneumonitis thought to be most consistent with hypersensitivity to nontuberculous mycobacteria. Cultures of water obtained from the patient's home shower were positive for Mycobacterium avium complex. The patient began substituting baths for showers, experiencing some gradual improvement of his symptoms. Subsequently, he installed point-of-use 0.2 micron membrane filters on his shower, and resumed regular showering after installation with continued symptomatic improvement. CT scans at 3 and 18 months revealed improvement and resolution, respectively. Four years later, he continues to shower in filtered home shower water and remains clinically well.

Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation.

Schistosoma mansoni infection has been associated with protection against allergies. The mechanisms underlying this association may involve regulatory cells and cytokines. We evaluated the immune response induced by the S. mansoni antigens Sm22.6, PIII and Sm29 in a murine model of ovalbumin (OVA)-induced airway inflammation. BALB/c mice were sensitized with subcutaneously injected OVA-alum and challenged with aerolized OVA. Mice were given three doses of the different S. mansoni antigens. Lung histopathology, cellularity of bronchoalveolar lavage (BAL) and eosinophil peroxidase activity in lung were evaluated. Immunoglobulin (Ig)E levels in serum and cytokines in BAL were also measured. Additionally, we evaluated the frequency of CD4+forkhead box P3 (FoxP3)+ T cells in cultures stimulated with OVA and the expression of interleukin (IL)-10 by these cells. The number of total cells and eosinophils in BAL and the levels of OVA-specific IgE were reduced in the immunized mice. Also, the levels of IL-4 and IL-5 in the BAL of mice immunized with PIII and Sm22.6 were decreased, while the levels of IL-10 were higher in mice immunized with Sm22.6 compared to the non-immunized mice. The frequency of CD4+FoxP3+ T cells was higher in the groups of mice who received Sm22.6, Sm29 and PIII, being the expression of IL-10 by these cells only higher in mice immunized with Sm22.6. We concluded that the S. mansoni antigens used in this study are able to down-modulate allergic inflammatory mediators in a murine model of airway inflammation and that the CD4+FoxP3+ T cells, even in the absence of IL-10 expression, might play an important role in this process.

Case study: the challenges of self-management of exacerbation of pulmonary symptoms.

PURPOSE: This case study demonstrates the signs and symptoms of pulmonary exacerbation and the challenges of self-management for a female veteran. DATA SOURCES: Data were obtained through the author's clinical practice in primary care nursing and research literature sources. DATA SYNTHESIS: The appropriate nursing diagnosis, nursing interventions, and patient outcomes were identified through the use of NANDA-International, the Nursing Interventions Classification, and the Nursing Outcomes Classification. CONCLUSIONS: This case study illustrates the appropriate nursing diagnosis, interventions, and outcomes pertinent to an individual with pulmonary exacerbations. It provides a framework for nurses in primary care when caring for individuals with pulmonary exacerbations. IMPLICATIONS FOR NURSING PRACTICE: Employing the NANDA-International standardized nursing diagnoses, the Nursing Interventions Classification and the Nursing Outcomes Classification provided the needed constructs for improving care for a patient that had pulmonary issues in a primary care setting.

[Allergic alveolitis after influenza vaccination]. / Allergische Alveolitis nach Grippeschutzimpfung.

Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.

Suppression of Th1 and Th17, but not Th2, responses in a CD8(+) T cell-mediated model of oral tolerance.

The role of CD8(+) T cells in oral tolerance remains unclear. To address this, we developed a model to induce CD8(+) Tregs by feeding the major histocompatibility complex class I immunodominant epitope of OVA, OVA((257-264)). OVA((257-264)) feeding induced tolerance similar to that observed in OVA protein-fed mice, capable of suppressing the production of Th1 and Th17 cytokines and inhibiting a Th1-driven delayed-type hypersensitivity response following immunization with whole OVA (wOVA) protein. OVA((257-264)) peptide-induced suppression could be transferred to naive mice with CD8(+) cells, but not CD8-depleted cells, isolated from mesenteric lymph nodes of peptide-fed mice. Interestingly, while capable of inhibiting Th1 and Th17 responses, OVA((257-264)) feeding could not suppress any feature of a Th2 inflammatory response, though OVA protein feeding could, suggesting that these cells function through a different mechanism than their CD4(+) counterparts generated in response to feeding with wOVA. Thus, CD8(+) T cells are functionally capable of mediating tolerance to Th1 and Th17 responses.