How Do We Catch Colds?

Samet, Jonathan M

“Colds,” upper respiratory tract illnesses, strike adults and children about twice each year, causing substantial discomfort, absenteeism, and economic losses. While some responsible viruses have long been known, uncertainty remains as to the mode of transmission, a topic little studied since the 1960s and 1970s (1). The available evidence has been interpreted as indicating that most transmission is by contact, although some studies favor aerosol transmission (1-5). Further evidence that could resolve this uncertainty has been needed, as control strategies would differ for the direct contact and aerosol transmission modes.

In this issue of the Journal (pp. 1187-1190), Myatt and colleagues (6) report two lines of evidence suggesting aerosol transmission of rhinoviruses. Their laboratory was three mechanically ventilated office buildings. Over a 20-month period they collected air samples for polymerase chain reaction analyses for rhinoviruses and enteroviruses, tracked CO2 concentrations as an index of the rate of exchange between indoor and outdoor air, and cultured volunteers with colds for respiratory viruses. The findings supporting aerosol transmission include: a positive association between CO2 concentration, a higher level indicating less air exchange, and the rate of virus detection in air; and isolation of the same rhinovirus, based on nucleic acid sequence, from the air of one building and a nasal lavage specimen in an individual with a cold during the same week.

Of course, many respiratory infections are spread by the inhalation of aerosolized pathogens in the form of droplet nuclei-tuberculosis and measles, for example. The earlier studies on mode of transmission of rhinoviruses, however, suggested that hand contact was the route of transmission. The evidence included experiments involving comparison of different modes of exposure, and the finding that small- and large-particle aerosols generated by coughing and sneezing infrequently contained the pathogenic viruses (1-3). In an appendix to their new report, Myatt and coworkers (6) show that one key experiment performed by Gwaltney and colleagues (3) had a substantial probability of not finding evidence for aerosol transmission because of the small numbers of exposed volunteers. Additionally, the experimental designs in some experiments may have favored contact over aerosol transmission; in one protocol, for example, donors contaminated their fingers with nasal secretions and then touched recipients’ hands for ten seconds, after which recipients touched their noses and conjunctivae (3).

Modern buildings-the location of much contact between infected and well persons-typically are sealed and have central heating, ventilating, and air conditioning (HVAC) systems. The HVAC system could disseminate infectious organisms as it moves air through the buildings. Air is delivered through ducts to spaces and returned to the HVAC system where some amount of outdoor air is added, and the air may be filtered and conditioned for temperature and humidity. The extent of air exchange depends on outdoor temperature, building design, and building management. Building ventilation codes are grounded in standards developed by the American Society of Heating, Refrigerating, and Air Conditioning Engineers (ASHRAE) (7). These standards have long been based on comfort but not on health considerations (8). The finding by Myatt and colleagues (6) of increasing virus detection with rising CO2 concentration indicates one possibility for reducing transmission-increasing exchange of indoor with outdoor air.

Understanding of the mode of transmission is critical for reducing transmission of infections within building environments, where large numbers of people may be in close proximity, contaminating surfaces with pathogens and generating infectious aerosols. Dramatic epidemics with emerging infections, like SARS, and the threat of using infectious organisms as a source of bioterrorism, like the spread of anthrax spores in the 2001 episode, add to the rationale for studies on transmission of infectious diseases within modern, often complex buildings. Strategies for controlling infections would differ, depending on the route of transmission: hand washing and cleaning of surfaces for contact and surface transmission and increasing ventilation and air cleaning for airborne transmission.

What approaches can be used to reduce the rate of transmission of airborne infections within buildings? The answer lies, in part, in the size of the infectious airborne particles. In articles published in the 1930s and 1940s, Wells (9, 10) described the generation of aerosols as infected persons coughed and sneezed; larger droplets quickly fall to the ground but the evaporation of moisture from droplets in a critical size range generates droplet nuclei. These particles are in an inhalable size range, less than 5 µm in aerodynamic diameter, and remain suspended in the air. Myatt and colleagues (6) sampled particles in this size range, implying that rhinovirus may exist on droplet nuclei.

Control strategies for infectious agents present in droplet nuclei, other than isolation, include increased ventilation of buildings, air cleaning, and sterilization of the air. Insufficient ventilation per person has been associated with higher infection rates (11, 12), but increasing exchange of outdoor with indoor air is inefficient for reducing infection risk. Filtration of large volumes of air for respirable particles is also impracticable. Wells proposed using UV irradiation to sterilize air and tested its use in schools in the late 1930s (10). The use of UV germicidal irradiation was more recently discussed by Riley and Nardell (13) for controlling transmission of tuberculosis, which takes place through droplet nuclei. Menzies and colleagues (14) performed a crossover trial of UV irradiation of air within the HVAC system of three office buildings. When the UV radiation was in use, microbial agent concentrations were lower in the supply air and workers had fewer work-related symptoms. We lack comparative studies that would guide the selection of building air quality management strategies to reduce optimally the burden of building-related respiratory infections.

Myatt and colleagues (6) have brought new methods to an old problem and gained novel insights that have possible public health implications. I agree with their call for extension of their methods to other environments, particularly schools. Their findings, coming from three buildings and the fortuitous identification of the same virus in one air sample and one nasal lavage sample, need replication.

Conflict of Interest Statement: J.M.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

References

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7. American Society of Heating Refrigerating and Air Conditioning Engineers (ASHRAE). Standard 62-2001: ventilation for acceptable indoor air quality (ANSI approved). Atlanta, GA: ASHRAE; 2001.

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9. Wells WF. On airborne infection. Study II. Droplets and droplet nuclei. Am J Hyg 1934;20:611-618.

10. Wells WF, Wells MW, Wilder TS. The environmental control of epidemic contagion. I: an epidemiologic study off radiant disinfection of air in day schools. Am J Hyg 1942;35:97-121.

11. Brundage JF, Scott RM, Lednar WM, Smith DW, Miller RN. Building-associated risk of febrile acute respiratory diseases in army trainees. JAMA 1988;259:2108-2112.

12. Hoge CW, Reichler MR, Dominguez EA, Bremer JC, Mastro TD, Hendricks KA. An epidemic of pneumococcal disease in an over-crowded, inadequately ventilated jail. N J Med 1994;331:643-648.

13. Riley RL, Nardell EA. Clearing the air: the theory and application of ultraviolet air disinfection. Am Rev Respir Dis 1989;139:1286-1294.

14. Menzies D, Popa J, Hanley JA, Rand T, Milton DK. Effect of ultraviolet germicidal lights installed in office ventilation systems on workers’ health and wellbeing: double-blind multiple crossover trial. Lancet 2003;362:1785-1791.

DOI: 10.1164/rccm.2403002

JONATHAN M. SAMET, M.D., M.S.

Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland

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