Jay M. Portnoy

Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Health effects of indoor fungi

OBJECTIVE To review the nontoxic harmful effects that poor indoor air quality caused by fungi can have on health. DATA SOURCES We searched PubMed for publications related to the various topics discussed in this review, and we relied on our knowledge of the field. STUDY SELECTION Where more than one publication was relevant, we attempted to identify a consensus of the reports and cited the most relevant articles. Priority was given to randomized controlled trials and expert reports when available, although much of the information herein relates to laboratory research. RESULTS Actively growing fungal colonies can release volatile substances that have an unpleasant smell, leading to psychological responses in the occupants such as fatigue and nausea. Symptoms that are likely caused by indoor fungi include respiratory complaints that involve the nose and lungs, eye symptoms, and mucous membrane irritation. These adverse effects can occur by a variety of mechanisms, including IgE-mediated hypersensitivity, fungal infection, irritant reaction to spores or fungal metabolites, and possibly toxic reaction to mycotoxins. CONCLUSIONS Reduced fungal exposure can reasonably be expected to improve health. Removal of moisture from the indoors and proper maintenance of air filters can aid in prevention and elimination of fungi from the home environment. Small areas of present contamination can be cleaned with a dilute bleach solution, which kills viable colonies and removes their mycelia. If fungal contamination is not addressed early, substantial damage can occur, requiring professional remediation. Above all, the individual should not panic at the first sight of fungi growing in the home. Regular inspection and cleaning can prevent many fungus-related problems.

Are our impressions of allergy test performances correct

BACKGROUND The clinical diagnosis is often subjective and susceptible to bias, yet it is the primary standard by which diagnostic tests are judged. Consequently, our opinions regarding various diagnostic tests may not be entirely accurate. OBJECTIVE To investigate the accuracy of the clinical history compared with concordant skin and quantitative specific IgE (s-IgE) measurements. METHODS Consecutive, consenting patients (N = 152) at 2 different allergy centers were examined by history and physical examination (HPE) alone to determine their sensitivity to 7 common allergens. Results were classified as positive, negative, or indeterminate. The HPE results were then compared to concordant skin prick testing (SPT) and s-IgE measurements and to quantitative IgE antibody measurements with and without knowledge of the SPT results. RESULTS Diagnosis by HPE deviated considerably from concordant SPT and s-IgE results. This deviation differed between allergists and allergens, reflecting a positive HPE bias that averaged 22%. Seventy-six percent of the HPE results judged indeterminate were resolved as negative. Using additional information from the quantification of s-IgE antibodies, considerable differences between the sites in the level of s-IgE associated with a positive HPE result with and without SPT results were observed. CONCLUSIONS Relative to the SPT and quantification of s-IgE antibodies, the diagnosis by HPE alone to common allergens is not consistent. Discrepancies were dependent on both allergen and allergist. The quantitative s-IgE data revealed that allergists use available information from the HPE and SPT differently. Since the HPE is the primary standard used in judging test efficacy (sensitivity and specificity), our current impressions of test performances are not likely to be accurate.

Allergenic materials in the house dust of allergy clinic patients

INTRODUCTION Environmental agents including animal, fungal, tree, and weed antigens are known to cause allergic rhinitis and asthma. The following study was performed to measure the antigen concentration of several of these in house dust of children seen in an allergy clinic. Comparisons are made between household allergen levels of children seen for asthma and children seen for other reasons. METHODS Dust samples were solicited from patients in a pediatric allergy specialty clinic and other individuals associated with the clinic. Persons submitting dust were asked to complete a questionnaire describing their house. Samples were extracted, centrifuged, and filtered for sterility. Samples were stored in 50% glycerol at -20 degrees C. Specific antigens for Alternaria, Cladosporium, Aspergillus, Candida, Dermatophagoides farinae, cat, dog, oak, fescue, ragweed, plantain, and cockroach were measured using inhibition assays developed with whole antigen extract. Allergens Der p1, Der f 1, Alt a 1, and Alt a 70 kD were measured using double monoclonal antibody assays. RESULTS Significant concentrations of whole antigen from cat, dog, oak, Alternaria, and Cladosporium were detected. Between 0.1 and 18 microg of Der f1 and Der p1 per gram of dust were also measured. Alt a 1 and Alt a 70 kD levels varied between 3.0 and 1000 U/g of dust. Significant positive correlations were observed in levels of dust mite and Alternaria allergen for patients with an evaluation of asthma. CONCLUSIONS We found measurable levels of fungal antigens (Alternaria, Cladosporium), mite antigens, and animal antigens (dog and cat) in the majority of dust samples in this self-selected set of allergy clinic patients. Specific allergens Alt a 1, Alt a 70kD, and Der p 1 were significantly higher in the homes of asthmatic patients when compared with patients seen for reasons other than asthma. These studies support the hypothesis that fungal allergen exposure is an important component in the pathogenesis of the clinical condition known as asthma.

Evaluation of Four Bioaerosol samplers in the Outdoor Environment

INTRODUCTION A comparative evaluation of four air samplers was performed using bioaerosol collection in the outdoor environment. METHODS Test samplers used included a Rotorod, a Kramer-Collins suction trap, an all-glass impinger (AGI-30), and a high-volume cyclonic liquid impinger (SpinCon). All samples were analyzed microscopically for spores and pollen. The two collectors providing a liquid sample (AGI-30 and SpinCon) also were analyzed for specific allergen content by enzyme-linked immunoassay. RESULTS The SpinCon collected a larger number of spores than the other devices. The number of spores collected by this unit per volume of air sampled was comparable to the AGI-30. The Rotorod and Kramer-Collins collected a lower number of spores per unit of air but collected a larger number of pollen grains per volume sampled. Alternaria allergens Alt a I and GP70 were collected by both liquid impingers; however, the SpinCon collected more Alt a I and the AGI-30 collected more GP70. CONCLUSIONS The SpinCon is a device that is capable of efficiently sampling a high volume of air and concentrating it in a form that can be analyzed for the presence of spores and fungal allergens. It is less useful for collecting intact pollen grains. Pollen allergen quantitation has not yet been performed on the SpinCon effluent.

Comparison of outdoor allergenic particles and allergen levels

INTRODUCTION Spore and pollen counts have been used traditionally to determine aeroallergen exposure. Using a liquid based collector and enzyme immunoassays, we have developed methods for measuring airborne allergen concentrations. In this work we test the hypothesis that airborne allergen concentrations are directly related to spore and pollen counts. METHODS Test samplers used included a high-volume cyclonic liquid impinger (SpinCon) and a standard spore trap (Burkard). Samples were collected on a weekly basis from May to October and were analyzed microscopically for spores and pollen grains. The liquid samples were analyzed by enzyme-linked immunoassay for the presence of allergens from Alternaria, Cladosporium, Aspergillus, oak, fescue, ragweed, and plantain. Specific Alternaria allergens Alt al and GP70 also were measured. RESULTS Pollen counts for the SpinCon and Burkard collectors were similar, though spore counts were lower with the SpinCon. Detectable amounts of three of the seven allergenic species including fescue, ragweed, and Alternaria were present in air samples. Concentrations of pollens were seen in their respective seasons while fungal allergen levels varied throughout the period. Allergen levels generally agreed with particle counts, however peak allergen levels and peak particle counts for individual species did not correlate well. CONCLUSIONS At flow rates of 236 L/min, the SpinCon is comparable to the Burkard for counting airborne pollen and spores. Samples collected by the SpinCon permit quantitative determination of allergen levels in outdoor air. The poor correlation between measured airborne allergen and related particles indicates the potential for significant allergen exposure in the absence of identifiable particles in air.

Rush Immunotherapy: Experience with a One-Day Schedule

INTRODUCTION Rush immunotherapy is a method for rapidly desensitizing patients to inhalant allergens. The frequency of systemic reactions during rush immunotherapy is similar to conventional immunotherapy when premedication is used. The most rapid protocol for rush immunotherapy reported to date requires one and one-half days which is inconvenient to patients and clinic schedules. To improve this situation and decrease the cost of giving rush immunotherapy, we have developed a 1-day protocol. METHODS for this ongoing study, 22 allergic patients received rush immunotherapy consisting of eight injections over six hours followed by two hours of observation in an outpatient clinic. Five had rhinitis and the rest has asthma, seven of whom were steroid-dependent. All were premedicated with astemizole, ranitidine, and prednisone for three days including the day of rush immunotherapy, and peak expiratory low rates were monitored. RESULTS Systemic reactions were seen in five of 22 (23%). They occurred following the sixth injection (1), seventh injection (2), or the final one (2) and consisted primarily of rhinitis or pulmonary symptoms with one episode of mild anaphylaxis. A systemic reaction was seen in only one steroid-dependent asthmatic patient. A local reaction preceded a systemic reaction in only one patient. All but three reached a maintenance dose in one day. All systemic reactions responded to epinephrine and all patients could go home after rush immunotherapy. Only one patient had a systemic reaction during the three months after rush immunotherapy. CONCLUSION One day rush immunotherapy is tolerated by most patients with a systemic reaction rate comparable to conventional immunotherapy. All patients were able to reach a maintenance dose months sooner than weekly schedules. With refinement of this procedure, rush immunotherapy may become a widely used method for desensitizing patients with inhalant allergens, and could make immunotherapy less expensive and more convenient.

IgE-reactive proteins from Stachybotrys chartarum.

BACKGROUND Stachybotrys chartarum has been associated with idiopathic pulmonary hemorrhage in infants. This is thought to be mycotoxin-related. There are increasing numbers of reports linking this fungus to the indoor environment of patients with other pulmonary problems, including allergies and asthma. OBJECTIVE Given the potential significance of this fungus as a pulmonary pathogen, this work evaluates the antigenic proteins of S. chartarum as to their molecular size and the prevalence of immunoglobulin (Ig)E and IgG directed against them in the general population. METHODS S. chartarum was isolated from a local home. S. chartarum for extract production was grown on minimum salts and glucose. Plasma from 132 healthy individuals was evaluated for IgE and IgG directed against S. chartarum using direct and inhibition enzyme immunoassay. The number and molecular size of those proteins that were bound by IgE from pooled sera known to contain IgE to S. chartarum were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting. RESULTS Enzyme immunoassay indicated 65 of 132 (49.2%) sera tested contained IgG against S. chartarum and 13 of 139 (9.4%) sera tested contained IgE against S. chartarum. Pooled sera identified two IgE-binding proteins from extracts of S. chartarum spores and mycelia. These proteins are 34 and 52 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblot. CONCLUSIONS We conclude sensitivity to S. chartarum is potentially much more widespread than previously appreciated. This fungus may impact the asthmatic and allergic population through both immunologic and toxic mechanisms. Its significance in the milieu of allergenic fungi may need to be re-evaluated.

The effect of temperature, relative humidity and rainfall on airborne ragweed pollen concentrations

Major weather parameters have long been known to alter airborne pollen and spore concentrations. The following study was conducted to study the effect of three of these parameters on airborne ragweed pollen concentrations.During the ragweed (RW) season for the years 1997 and 1998, 10 minute pollen collections were taken at least every 4 hours using an Allergenco MK-3 spore trap. Slides were fixed, and counted microscopically at 400X. During this same period, weather parameters were monitored by an Automated Weather Systems recording station located within a few meters of the collector.The ragweed season for this region begins in mid August and ends by mid October. Temperature patterns for the period demonstrated usual daily fluctuations with highs 13 to 35 °C and lows 8 to 24 °C. Relative humidity readings for the period varied between 25 and 100%. Highest RW values were seen after seasonal cooling in September. Daily rainfall for the period varied between 0 and 100 mm. Airborne RW always declined sharply after strong rainfall events (> 10 mm/day). Peak airborne RW concentrations were often associated with the passing of frontal boundaries and the change in wind direction and velocity that accompanies that passing.Factors influencing airborne RW concentrations are multiple and complex, but atmospheric forces have great influence. The passing of major weather fronts and the associated temperature drops, wind disturbances and rainfall are the major factors.

The effect of time and extraction buffers on residual protein and allergen content of extracts derived from four strains of Alternaria

BACKGROUND A series of studies was performed to identify optimal elution conditions for production of desired Alternaria allergens with simultaneous reduction of undesired ones. METHODS Proteins and allergens from four strains of Alternaria extracted for differing time intervals and in different buffers were analyzed by one- and two-dimensional electrophoresis, as well as by immunoglobulin E enzyme-linked immunosorbent assay inhibition and immunoblotting. RESULTS The amount of protein and carbohydrate released varied with each time interval but was consistent between buffers. Extracts from longer time intervals tended to contain more carbohydrate. Electrophoresis of the four strains demonstrated many similar proteins; however, the concentrations of these proteins showed considerable interstrain difference. Comparison of extraction times for single strains by immunoblotting showed that certain allergens are preferentially released during specific time intervals. Some allergens were seen to be most prevalent in a 24-hour extract, whereas others were most prevalent in a 1-hour extract. Two-dimensional electrophoresis resolved bands into discrete spots. The major shared elements of the four strains could be easily identified. The appearance and disappearance of individual protein elements with time was seen. CONCLUSIONS Elution conditions have a significant impact on quantities of specific glycoproteins contained in extracts of Alternaria and must be controlled and optimized when such extracts are produced for allergen purification.