Gabriel Reboux

Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria

Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers. 13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, including Mycobacterium immunogenum. M. immunogenum was identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract from M. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established. The detection of specific antibodies against M. immunogenum Ag at high levels in case sera suggests that M. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.

Indoor mold concentration in Eastern France

UNLABELLED Our prospective case-control study of 118 dwellings in Eastern France examined fungal contamination in unhealthy dwellings (n = 32) (homes with visible mold contamination and adverse health outcomes reported by the occupants), dwellings occupied by allergic patients (with medical diagnostic and positive prick-tests for molds) (n = 27) and matched control dwellings (n = 59). Unhealthy dwellings present higher airborne concentrations of Aspergillus, Penicillium, and Cladosporium than control dwellings, irrespective of the room sampled. Bedroom walls were more highly contaminated by molds than others. Dwellings occupied by allergic patients differed significantly for airborne concentrations of Penicillium only, but not for wall surface contamination, whereas bathroom walls were more highly contaminated than other rooms. Molecular identification of 12 Penicillium species showed Penicillium chrysogenum and Penicillium olsonii to be the two main species. From the total average of molds, by impaction method, useful thresholds can be given: below 170 CFU/m(3), between 170 and 560 CFU/m(3), 560 and 1000 CFU/m(3) and above 1000 CFU/m(3), respectively for dwellings with low, moderate, high, and very high concentrations. The latter would be considered a potential health hazard. PRACTICAL IMPLICATIONS A single measure of airborne concentrations of molds by impaction allows to establish useful thresholds by social services to estimate in a objective way the housing moldiness. Excluding the summer period, reproducibility of this kind of measure on 3 months, in the fixed limits, is 94.3%. The differences in terms of biodiversity of the unhealthy housing and those accommodating allergic patients imply a specific approach to decrease fungi airborne concentrations. The biodiversity of Penicillium raises the problem of the use of the single extract of Penicillium chrysogenum for skin-tests. The extent of the contaminated surfaces must be measured to assess the potential risk linked to spore contamination. Indeed, surface sampling mostly allows qualitative assessment of the environment.

Characteristics of dwellings contaminated by moulds

Dwellings showing a presence of moulds are considered to be unhealthy both by the inhabitants and by sanitary authorities. Although the thresholds of pathogenicity have not yet been established, the toxic, allergic and infectious risk of indoor moulds is better understood today. A study on indoor fungi contamination for 128 dwellings was done between October and May in France. It concerned 69 dwellings, the occupants of which either complained to the sanitary authorities about problems of moulds and humidity or consulted a doctor who related their symptoms to housing conditions. Fifty-nine other dwellings, the occupants of which were healthy, constituted the control group. We present the statistical analysis of questionnaires, which aimed to clarify characteristics of dwellings associated with high concentrations of airborne moulds. Air samples were taken with an impactor in 500 rooms. On visiting dwellings, investigators obtained answers to 25 questions concerning characteristics of inhabitants and living space, as well as the presence of mould indicators. Indoor and outdoor temperature and indoor relative humidity of air measurements were taken. The total concentration of fungi in the air was significantly higher in ground floor apartments versus those on other floors (p = 0.047), in small and highly occupied dwellings (p = 0.03 and 0.003), in dwellings with electric heating (p = 0.04), without a ventilation system (p = 0.003), with water damage (p = 0.003), and finally, in those where the investigator noted an odour of moisture or visible moulds (p < 0.001). The efficacy of the latter criteria in the evaluation of insalubrity is discussed.

Indoor fungal contamination of moisture-damaged and allergic patient housing analysed using real-time PCR.

Aims:  The aim of our study was to compare, using real‐time (Rt) PCR, quantitative levels of five fungal species in three kinds of dwellings.

Indoor fungal contamination: Health risks and measurement methods in hospitals, homes and workplaces

Abstract Indoor fungal contamination has been associated with a wide range of adverse health effects, including infectious diseases, toxic effects and allergies. The diversity of fungi contributes to the complex role that they play in indoor environments and human diseases. Molds have a major impact on public health, and can cause different consequences in hospitals, homes and workplaces. This review presents the methods used to assess fungal contamination in these various environments, and discusses advantages and disadvantages for each method in consideration with different health risks. Air, dust and surface sampling strategies are compared, as well as the limits of various methods are used to detect and quantify fungal particles and fungal compounds. In addition to conventional microscopic and culture approaches, more recent chemical, immunoassay and polymerase chain reaction (PCR)-based methods are described. This article also identifies common needs for future multidisciplinary research and development projects in this field, with specific interests on viable fungi and fungal fragment detections. The determination of fungal load and the detection of species in environmental samples greatly depend on the strategy of sampling and analysis. Quantitative PCR was found useful to identify associations between specific fungi and common diseases. The next-generation sequencing methods may afford new perspectives in this area.

Hypersensitivity Pneumonitis Due to Molds in a Saxophone Player

This 48-year-old patient was evaluated for an interstitial pneumonia. An open-lung biopsy showed a pattern of nonspecific interstitial pneumonia. The CT scan appearance, showing mosaic ground-glass opacities in the ventilated parts of the lung, the centrolobular predominance of inflammation on the lung sections, and the presence of a lymphocytic alveolitis at BAL suggested a hypersensitivity pneumonitis. The patient was a white-collar worker and had no contact with pets, birds, drugs, or molds at home. He used to play the saxophone as a hobby. Two molds, Ulocladium botrytis and Phoma sp, were detected in the saxophone. Precipitating antibodies to these molds were present in his serum. An additional study confirmed the frequent colonization of saxophones with potentially pathogenic molds, such as Fusarium sp, Penicillium sp, and Cladosporium sp. Respiratory physicians should be aware of the risk of hypersensitivity pneumonitis in saxophone or perhaps other wind instrument players.

[Moulds in dwellings: health risks and involved species].

INTRODUCTION In industrialized countries the population spends 90% of its time in enclosed spaces. Since 1973, energy consumption for heating decreased on average by 36% per dwelling. Low-quality insulation, a fall in temperature and inadequate ventilation translated into high humidity in dwellings, which led to proliferation of moulds. BACKGROUND The allergenic, toxic and infectious effects of moulds on human health are documented. However, the potential dose/effect relationship between measured concentrations of indoor moulds and respiratory disorders often remains difficult to assess accurately. In several cases, fungi were demonstrated only as a promoter of health disorders. In a few cases (hypersensitivity pneumonitis, invasive fungal infections), the pathogenesis is without doubt due to environmental fungal exposure in a limited number of patients. On the other hand, the role of fungi was suspected but not proven for some well-defined pathologies, and some ill-defined health disorders, affecting large numbers of patients, such as the Sick Building Syndrome, rhinitis, sinusitis and conjunctivitis, as well as asthma and exacerbations of bronchitis. Eighteen fungal species, suspected of playing a role in public health, have been listed by the French Superior Council of Public Health. For each species, the proliferation conditions, type of substrates contaminated and heath effects reported in the literature are described. VIEWPOINT The lack of standardization of measurements of concentrations of fungal species, the interactions with chemical compounds (formaldehydes), organic compounds (mycotoxins, endotoxins) and between species, makes the analysis of indoor fungal contamination complicated. The time has come to establish clearly a relationship between exposure to fungi and health disorders, rather than continuing to investigate factors related to the level of indoor fungal contamination.

Farmer’s Lung Disease and Microbiological Composition of Hay: A Case–Control Study

Previous studies performed in France have suggested that handling hay contaminated with high amounts of moulds, and especially Absidia corymbifera and Eurotium amstelodami, may favour farmer’s lung disease. The circumstances favouring farmer’s lung disease and the distinctive microbiological composition of hay samples that provoke attacks need to be specified. We present a case–control study which investigates the agricultural practices and the microbiological composition of hay handled in patients with farmer’s lung disease as compared to those of a representative control population. Ten cases identified the hay they were handling at the onset of symptoms. The location, type of farm and working conditions were similar to those of the control farms. Conversely, the microbiological composition of hay differed, with significantly higher amounts of E. amstelodami (P < 0.01), A. corymbifera (P = 0.003), mesophilic Streptomyces (P < 0.01), thermophilic Streptomyces (P < 0.01) and Saccharomonospora viridis (P < 0.01) than in the control population. Our results demonstrate that hay identified by patients as having a harmful effect is characterized by a higher total amount of microorganisms, notably five microorganisms that seem discriminative. Mean concentrations are 2- to 115-fold higher in hay suspected to cause symptoms than in hay from a representative panel of farms. Handling hay with high amounts of these five microorganisms constitutes a risk factor for farmer’s lung disease that should be considered for the development of prophylactic measures.

Longitudinal study of anti-Candida albicans mucosal immunity against aspartic proteinases in HIV-infected patients

Summary: Oropharyngeal candidiasis (OPC), mainly caused by Candida albicans, is commonly observed in HIV‐infected patients. Secreted aspartic proteinases (Saps) are virulent agents involved in adherence to the mucosal surface and in tissue invasion. The immune secretory response to these agents was investigated in 15 HIV‐infected patients, during oral yeast colonization and episodes of oropharyngeal candidiasis (OPC), in a 1‐year longitudinal study. We developed an avidin‐biotin‐amplified immunofluorometric assay for the detection of specific immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens. We report increases in anti‐somatic, anti‐Sap2, and anti‐Sap6 salivary antibodies in patients with OPC. Over the 1‐year period, not only OPC episodes but also variations in yeast colonization levels were correlated with variations in salivary anti‐Sap6 antibody levels. Our results show the ability of HIV‐infected patients to produce high levels of salivary antibodies; however, these antibodies were not efficient in limiting candidal infection, probably because of cellular cooperation deficiency and the enhanced virulence of the infecting strain.

Azole-Resistant Aspergillus fumigatus Isolate with the TR34/L98H Mutation in Both a Fungicide-Sprayed Field and the Lung of a Hematopoietic Stem Cell Transplant Recipient with Invasive Aspergillosis

ABSTRACT A French farmer developed invasive aspergillosis with azole-resistant Aspergillus fumigatus with the TR34/L98H mutation following a hematopoietic stem cell transplantation. He had worked in fungicide-sprayed fields where a non-genetically related A. fumigatus TR34/L98H isolate was collected. If azole resistance detection increases, voriconazole as first-line therapy might be questioned in agricultural areas.