By Michelle L. North, PhD; Neil E. Alexis, PhD; Anne K. Ellis, MD MSc; Chris Carlsten MD, MPH
The October issue of Annals of Allergy, Asthma & Immunology (published by the American College of Allergy, Asthma & Immunology) featured a CME review entitled “Air pollution and asthma: how can a public health concern inform the care of individual patients?” To those of us who don’t practice medicine, and have no responsibility to keep up certification by continually learning new material, the CME process is a bit mysterious. Fortunately, two of the authors of this article, Drs. North and Ellis, are esteemed contributors to this website. We reached out to them to answer some questions on this article, which is a timely intersection of public health and individual health care. All four authors contributed to this Q&A. Out of consideration for the fact that three of them are Canada based, we have left the Canadian spelling of the word “mould.”
AAC: First of all, thank you all for taking the time to answer questions about your article.
How does the Annals of Allergy, Asthma and Immunology choose a subject for a CME Review like yours? If it was done at the impetus of you and your team, what prompted you to suggest it?

MN-NA-AKE-CC: The Annals was soliciting ideas for CME articles from editorial board members (including Dr. Ellis). Our team, including Dr. Michelle North, Dr. Neil Alexis, Dr. Anne Ellis and Dr. Chris Carlsten, decided to propose to focus on air pollution because it is a growing health problem. In addition to exacerbating asthma, air pollution contributes to the burden of disease from lung cancer, cardiovascular disease, stroke, and chronic obstructive pulmonary disease (COPD). Air pollution has serious economic consequences, imposes burdens on healthcare systems, and affects an individual’s quality of life. The field of air pollution research is very broad and continues to grow, but we are particularly interested in the connection between air pollution and asthma. Dr. Carlsten established the Air Pollution Exposure Laboratory (APEL) at the University of British Columbia for controlled human exposure to diesel exhaust and other inhalants. Dr. Alexis leads the Sample Acquisition and Repository Core for the University of North Carolina Center for Environmental Medicine, Asthma and Lung Biology, where he uses induced sputum to study inflammation in the lung associated with air pollution exposure, in close collaboration with the Environmental Protection Agency. Dr. Ellis and Dr. North have established a birth cohort in Kingston, Ontario, of approximately 400 mother/child pairs, to examine the connection between environmental exposures and the developmental origins of asthma/allergies. The negative effects of air pollution on asthma is a topic we are all passionate about, and it was a natural choice when the opportunity to write this article came about.
AAC: Your article begins with a patient vignette that illuminates the problem of translating broad insights on public health into individual health care. A professor from a rural area moves to an urban neighborhood and starts wheezing during her bicycle commute to work. Her doctor deduces that it is connected to the time of day and the volume of vehicular traffic. Why is this kind of storytelling so important to doctors who have been practicing for a long time?

MN-NA-AKE-CC: Case studies are important in medicine because they are meant to be instructive examples for physicians who might encounter patients with similar problems. The storytelling ‘feel’ of case studies mirrors the discussion that doctors have with their patients on a day-to-day basis, while they collect the patient history through questions and answers. The case study then takes you through some of the thought processes, logic and considerations the physician may go through while figuring out a treatment plan. Often case studies focus on rare diseases, uncommon presentations or adverse reactions. Case studies are important for establishing how the effects of exposures such as air pollution may affect individual patients. There is a serious lack of case studies that focus on air pollution and asthma. Perhaps they are lacking because, while they should be relatively common, air pollution is often difficult to identify as a root cause of an asthma exacerbation. In this case the physician was able to establish a convincing connection between traffic related air pollution and wheezing in the Professor, which is what made working on this case report exciting for us.
AAC: The scope of clean air legislation and regulation has steadily increased over the past half century as nasty-sounding particles and gasses are researched, as you point out. Your article mentions biological agents, both for themselves and for their synergistic effects in combination with things like ozone. Could you name some of these things, and tell us where patients might encounter things like endotoxin in their everyday lives?

MN-NA-AKE-CC: Some of the major types of bioaerosols are pollens, dust mites, particles of bacterial origin and particles of fungal origin.
Pollens
Pollens from trees, grass, weeds and other plants can migrate indoors through open windows. Pollen is not known to be harmful unless someone has an allergy to a specific type of pollen. To reduce outdoor pollen penetrance into a home, a well-sealed home with HEPA-filtered ventilation may help.
Dust Mites
Dust mites feed on organic matter such as flakes of human skin, and their feces contain potent allergens. The most common species of indoor dust mite is Dermatophagoides pteronyssinus. Bedding is the most important route of exposure. Dust mite exposure can be reduced through the use of impermeable mattress and pillow covers, and frequent laundering of bedding. Decreased humidity can also reduce dust mites.
Aerosols Originating from Bacteria
Particles of bacterial origin often include endotoxin. Endotoxin is a general term describing a group of chemicals produced by bacteria called lipopolysaccharides. Lipopolysaccharides are part of the outer membrane of Gram-negative bacteria, and they are large molecules consisting of a lipid (or fatty component) and a polysaccharide (a sugar component). Because our immune systems are built to fight bacterial infections, we react strongly to endotoxin. Endotoxin activates a wide variety of immune system cells and acts as a pyrogen (fever-inducer), if present in high enough concentrations in the body. Above a threshold level, inhalation of endotoxin causes neutrophilic inflammation in the airways and it can exacerbate pre-existing asthma. Some common environments in which people may encounter endotoxin include farms, especially in buildings that house livestock. Some people are exposed to endotoxin through occupational exposures, including cotton dust, swine dust (although swine dust-induced health effects are also associated with gram positive bacteria such as peptidoglycans), waste management or cleaning up after natural disasters such as hurricane Katrina. People who work with animals or who own rodents encounter endotoxin while changing the caging material. Cats and dogs have also been shown to increase endotoxin in homes, which can be reduced by keeping your pet and home clean and changing litter often.
Aerosols Originating from Fungi
Fungi are the most common microorganisms responsible for allergic disease. Indoor fungi are a mixture of those that grow indoors and those that enter from outside. In addition to allergenic proteins, fungi also produce volatile organic compounds (VOC’s), mycotoxins, and ?-glucans. VOC’s, produced by fungal growth as gaseous by-products, include hexane, methylene chloride, benzene and acetone. Controlled exposures to VOC’s have demonstrated that they induce mucous membrane irritation and asthma-like symptoms. Mycotoxins have long been known to pose health risks as food contaminants, and more recently respiratory effects have been recognized, including effects on immune system cells. The spores of some fungal species have a high content of mycotoxins, including trichothecenes (produced by “black mould”), ochratoxins and aflatoxins. ?-glucan is another component of fungal aerosols, derived from the fungal cell wall. ?-glucan possesses potent immune-cell activating effects, including inducing the production of cytokines and increasing IgE-mediated histamine release. Participants exposed to ?-glucan in experimental challenges reported symptoms of thirst and nose irritation, headache, fatigue and cough. In this context, ?-glucan does not appear to induce the robust inflammatory response observed with endotoxin. However, these types of studies may not represent the consequences of long-term exposures. Fungal allergens also contribute to the occupational illness “baker’s asthma”. While it is most often attributed to cereal flours (wheat, rye and barley), fungal allergens have now been found to play a significant role as well. There is a considerable body of literature associating asthma exacerbation, wheezing and cough, particularly in children, to residence in damp or water-damaged homes. Thus, reducing dampness and mould exposure in the home is likely to have health benefits. For pre-existing obviously mouldy areas, cleaning with a hypochlorite bleach and detergent solution while wearing a well-fitting mask will help to remediate the area. To prevent future mould growth, adequate outdoor air ventilation with filtration should be maintained throughout the year. Elimination of dampness and water leaks indoors is essential. Dust mite allergens have also been found to be present at higher levels in damp homes, and dampness in buildings can also increase the emission of VOC’s, due both to degradation of building material and increased fungal growth. Therefore the use of dehumidifiers (cleaned regularly) and/or air conditioning can reduce both fungal aerosols and dust mites.
AAC: Your discussion under the subhead “The Precautionary Principle” is very interesting. You state, “…we argue that our knowledge of this pressing public health issue has evolved to the point where physicians can integrate it into primary practice.” We have known about air pollution and asthma for decades. Why does it take so long for doctors to adopt such insights as part of their practice?

MN-NA-AKE-CC: The management of asthma is complex. Doctors consider choices of asthma treatment based on severity, triggers, co-morbid conditions, and age, and from there adjust medications depending upon the level of control achieved. These comorbid conditions include obesity, obstructive sleep apnea, rhinitis, sinusitis and gastroesophageal reflux. Depending on the individual, some of these issues may have a larger effect on their asthma control than air pollution. Air pollution is mentioned in the asthma guidelines, under the section on avoiding environmental factors that worsen asthma. However, besides air pollution, there are a variety of environmental factors that worsen asthma, including allergens, viral infections, and stress to name a few. Doctors are also concerned about counseling patients to avoid these additional factors. Also, there may exist in some segments of the physician population a tendency to treat with medications, which may seem more tangible than preventive approaches.
It took some time for the damaging effects of environmental exposures such as tobacco smoke to be recognized and fully taken up into clinical practice, but now doctors have been counseling patients for decades to quit smoking and to reduce their exposure to second hand smoke. In the case of tobacco smoke, the source of the exposure is easily identifiable. In contrast, air pollution can come from many sources, but it is invisible, and difficult to isolate as the primary cause of an exacerbation. Because in the particular case we presented, the doctor was able to identify air pollution as the primary cause of the Professor’s asthma exacerbation, presenting this case was an important opportunity to illustrate that sometimes it can be a major factor for an individual patient.
We think that the awareness of both physicians and patients are growing together with respect to this issue, and that is a good thing. If patients become more aware that air pollution can exacerbate their asthma, they will talk to their doctors about changes they might be making in their routine, travel, or work that could affect exposures, and ways they can minimize them. The hope is, it will help to bring these issues to the forefront and identify those times when air pollution reduction alone might be able to make a big difference in the patient’s asthma control.
AAC: Thank you for your time.
Michelle L. North, PhD Department of Biomedical & Molecular Sciences, Queen’s University, Allergy Research Unit, Kingston General Hospital, Kingston, Ontario, Canada; Neil E. Alexis, PhD Center for Environmental Medicine, Asthma, and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, Department of Pediatrics, University of North Carolina, School of Medicine University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Anne K. Ellis, MD MSc Department of Biomedical & Molecular Sciences, Allergy Research Unit, Division of Allergy and Immunology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada; Chris Carlsten MD, MPH Air Pollution Exposure Laboratory, Vancouver Coastal Health Research Institute, Vancouver General Hospital, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. Dr. North and Dr. Ellis’s previous posts for this website can be found here, here, and here.