Papers

Community study of role of viral infections in exacerbations of asthma in 9-11 year old children

^a University Medicine, Southampton General Hospital, Southampton SO9 4XY, ^b Department of Medical Statistics and Computing, University of Southampton, Southampton SO9 4XY, ^c Department of Microbiology, University of Leicester, Leicester LE1 9HN, ^d MRC Common Cold Unit, Salisbury

Correspondence to: Dr Johnston.

Abstract

Objective: To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community.
Design: Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses.
Subjects: 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire.
Setting: Southampton and surrounding community.
Main outcome measures: Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions.
Results: Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 1/min. The most commonly identified virus type was rhinovirus.
Conclusions: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.

Introduction

Patients having an acute attack of asthma often give a history of a "cold" before the onset of the exacerbation. Despite numerous studies, however, the cause of most exacerbations of asthma remains controversial. With the exception of asthma epidemics such as those associated with soya beans in Barcelona,¹ there is little evidence to implicate aeroallergens as provoking agents.^{2 3} The weighted average detection rates of viruses during exacerbations of asthma were 24% for incidental studies and 31.9% for prospective studies in children and 13.3% in adults.⁴ This compares with a rate of 3% in asthmatic patients when free of symptoms.^{5 6 7 8} Several studies have observed a temporal relation between viral infections and asthma exacerbations,^{9 10 11 12 13 14 15 16} while others have found associations between severity of wheezing illness and rate of viral detection.^{12 13 14 17 18} These studies are weakened by low rates of detection,^{11 14} particularly of rhinoviruses and coronaviruses, which together cause about two thirds of common colds,^{19 20} and by a lack of objective measures to define the exacerbations being studied. We conducted a detailed 13 month longitudinal study to investigate the association of viral infections with exacerbations of asthma in 9-11 year old children in Southampton using the polymerase chain reaction to increase sensitivity of detection.^{21 22}

Respiratory symptoms recorded during
the study

Upper respiratory        Lower respiratory
  symptoms                 symptoms

Runny nose               Cough during the day
Sneezing                 Cough during the night
Blocked or stuffy nose   Wheeze during the day
Itchy, sore, or watery   Wheeze during the night
  eyes                   Difficulty breathing or
Sore throat                shortness of breath
Hoarse voice             Not fit to go to school
Fever or shivery           because of chest
Headaches or face aches    problems (score 2)
Aches or pains elsewhere

Subjects and methods

We invited the 186 children aged 7-9 years from the Southampton area who had completed a previous study on bronchial hyperreactivity in children with wheeze or persistent cough,²³ to take part in a study on the role of viral infections in asthma. A total of 114 children, then aged 9-11 years (62 boys and 52 girls), enrolled for this study, which lasted 13 months from 3 April 1989 to 7 May 1990. Children or their parents recorded the peak expiratory flow rate twice daily, and daily upper and lower respiratory tract symptoms were scored from 1 (mild) to 3 (severe) and summated. The box lists the symptoms included. Parents telephoned the investigators if the upper or lower respiratory scores totalled 4 or more, if peak expiratory flow fell by more than 50 l/min from the child's usual value, or if the parent subjectively felt that the child was developing a cold. The child was then visited at home by one of the investigators within 48 hours to obtain specimens for virological testing. Drug treatment and baseline peak expiratory flow were assessed over the first two weeks of the diary card recordings. The study was approved by the Southampton hospitals joint ethics subcommittee.

After each report the investigator took a nasal aspirate and diluted it in 10 ml of virus transport medium,²¹ 8 ml of which was frozen in dry ice and stored at -70°C. The remainder was used to prepare six cytospin slides, which were fixed and stored at -20°C for later analysis. A 100 µl finger prick blood sample was taken at the time of the report and two to three weeks later. Serum was diluted and stored at 4°C.

We also asked children who had reported episodes to provide a further sample during June to September 1991, when they had not had any upper or lower respiratory symptoms in the preceding two weeks. Sixty five children agreed to provide samples. Rhinorrhoea was induced,²¹ and sampling and storage methods were identical to those described above.

DETECTION OF VIRUSES

Nasal aspirates were cultured in Ohio HeLa, HEp-2, and clone 16 cells.²⁴ Samples collected between 1 November 1989 and 18 January 1990 (during an influenza type A epidemic in Britain) were also cultured in MDCK cells, and if parainfluenza virus infection was suspected from the results of immunofluorescence or serology, aspirates were cultured in LLC-MK2 cells. The cytopathic effect of an isolate was confirmed by electron microscopy (coronavirus), acid stability testing (rhinovirus),²⁵ immunofluorescence (adenovirus, respiratory syncytial virus, and parainfluenza virus), or haemadsorption (influenza virus).²⁶

Picornavirus (rhinovirus and enterovirus) polymerase chain reaction--Duplicate 50 µl aliquots from all samples were taken from two tubes and analysed on different days. Reverse transcriptase polymerase chain reaction and internal probe hybridisation were carried out.²¹

The coronavirus polymerase chain reaction was used to analyse 80 samples with sufficient remaining clinical material in which no virus was detected after all other tests, 10 samples known to be positive for coronavirus (both 229E and OC43) by enzyme immunoassay, and 10 known to be positive for other viruses. The nested reverse transcriptase polymerase chain reactions used primers specific to the nucleocapsid genes of 229E or OC43.²² Samples were analysed singly with positive results confirmed in duplicate.

Immunofluorescence --Respiratory syncytial virus, adenovirus, and influenza virus type A were detected by direct immunofluorescence (Novo Biolabs, Cambridge). Parainfluenza virus types 1-3 were detected by indirect immunofluorescence with polyclonal antibodies against all three types (Barbara Young, Royal Victoria Infirmary, Newcastle). Testing was carried out on cytospins from nasal aspirates and the results confirmed on tissue culture cells.

Serology--We obtained antigens for enzyme immunoassays for coronavirus 229E and OC43 from the Medical Research Council Common Cold Unit; for respiratory syncytial virus, adenovirus, and parainfluenza virus type 1 from University Microbiology, Southampton; for parainfluenza virus types 2 and 3, from Virion, and for influenza virus type A from the Public Health Laboratory Service, London. Samples were analysed in duplicate except for parainfluenza virus type 2, influenza virus, and adenoviruses, which were analysed singly; equivocal or positive results were confirmed in duplicate. Standard methods were used, and a twofold rise in titre was taken as significant. For coronavirus, however, a difference of more than 2 standard deviations of log antibody units between acute and convalescent samples was used.²⁷

ANALYSIS OF DATA

The data from the whole 13 months for each child were plotted to allow visual inspection for patterns of illness (fig 1). All clinical data and virus detection results were coded and entered on to a computer and checked against originals.

View larger version (138K): [in this window] [in a new window]   FIG 1--Examples of charts of peak flow recordings and respiratory symptom scores for three children taking part in the study. The horizontal axis represents the 13 months of the study

An episode was defined as two or more days with symptom scores above the median for that child (or peak expiratory flow at or below the 10th centile) preceded by one day at or below the median (above the 10th centile) and followed by two days at or below the median (at or above the median). A reported episode of lower respiratory tract symptoms or fall in peak expiratory flow was considered to coincide with an observed episode if it occurred within seven days of the observed episode. For upper respiratory tract symptoms reported and observed episodes were considered to coincide if the reported episode was during or up to seven days after the observed episode. Severity was expressed as the maximum total score during the episode for upper and lower respiratory tract episodes and as the largest drop from the median expiratory flow rate for peak expiratory flow episodes. The duration of an episode was taken as the time from the initial fall in peak expiratory flow or rise in symptoms to the day when they returned to the median value.

Normally distributed data are summarised by mean (SD) and skewed data by median (interquartile range). The Mann-Whitney U test was used to compare continuous data between subgroups. Different episodes in the same child were treated as independent. Results were not altered by use of models including a random child effect to allow for non-independence of multiple episodes or reports from the same child. For the 65 children who had samples taken while asymptomatic the number of signals positive for picornavirus by polymerase chain reaction was compared in the asymptomatic samples and in the first symptomatic sample for each child by McNemar's test. Fortran programming was used to adjust peak expiratory flow for height²³ and to define episodes. Statistical analyses were done with the statistical package SPSS.

Results

A total of 108 children (58 boys) completed the study. Six children took bronchodilators regularly and 15 as required; 18 took prophylactic inhaled steroids or disodium cromoglycate; and three took theophyllines. The median baseline peak expiratory flow was 312 (264-350) l/min. Sixty two children were atopic,²⁸ 42 had had asthma diagnosed, and 52 had reported wheeze in the original questionnaire.²³

SYMPTOMS AND PEAK EXPIRATORY FLOW EPISODES

There were many unreported episodes of respiratory symptoms and diminished peak expiratory flow (fig 1, table I). During the 13 months the mean (SD) number of episodes per child was 4.13 (1.66) for a fall in peak expiratory flow, 5.33 (4.99) for lower respiratory tract symptoms, and 7.24 (4.47) for upper respiratory tract symptoms. The median (interquartile range) total duration of the episodes per child each year was 64 (44-79), 30 (11-56), and 39 (22-70) days respectively. The median number of days a year that lower respiratory tract symptom scores of at least moderate severity were recorded was 16 (7-35).

TABLE I--Number, type, severity, and duration of reported and
unreported episodes, from symptom and peak expiratory flow rate
diaries. Values are medians (interquartile ranges) unless stated
otherwise
------------------------------------------------------------------------------
Type of episode                 Reported       Unreported       Total
------------------------------------------------------------------------------
Upper respiratory tract:
 No of episodes                    253            529           782
 Duration (days)                7 (4-12)        4 (2-7)       5 (3-8)
 Severity (symptom score)       6 (4-8)         3 (2-3)       3 (2-5)
Lower respiratory tract:
 No of episodes                    200            376           576
 Duration (days)                7 (5-12)        4 (2-7)       5 (3-9)
 Severity (symptom score)       4 (3-7)         2 (1-3)       2 (2-4)
Peak expiratory flow:
 No of episodes                    153            293           446
 Duration (days)               14 (7-24)        8 (4-18)     10 (5-21)
 Severity (maximum fall from
 median, l/min)                81 (54-107)     43 (29-67)    52 (33-85)

The seasonal patterns of reported and unreported episodes were similar (fig 2). However, the severity and duration of reported episodes were significantly greater than those of unreported episodes (P<0.001, table I). The median maximal percentage fall from baseline in peak expiratory flow was 26% and 13.8% for reported and unreported episodes respectively. A fall of 30-120 l/min (9.6%-38.5% from baseline) was recorded in 120 (78%) reported peak expiratory flow episodes and a fall of over 120 l/min (>38.5% from baseline) in 26 (17%) episodes. Cough, wheeze, or shortness of breath of at least moderate severity was recorded in 169 (85%) of the reported lower respiratory tract symptom episodes.

View larger version (107K): [in this window] [in a new window]   FIG 2--Seasonal patterns of reported and unreported respiratory symptom and peak expiratory flow episodes

There were 292 reported episodes from 96 of the 108 children. The mean number of reports was 2.5 per child a year, and the maximum number of reports was eight (five children). Satisfactory (0.5-1.5 ml mucus) nasal aspirate samples were obtained from the children for all 292 reported episodes and for all 65 samples from children when asymptomatic.

The median delay between reduction in peak expiratory flow and onset of upper respiratory tract or lower respiratory tract symptoms was one day, the delay being two or more days in 54/117 (46%) upper respiratory and 39 (33%) in lower respiratory tract episodes. Lower respiratory tract and upper respiratory tract symptoms were usually reported on the same day, but upper respiratory tract symptoms preceded lower respiratory tract symptoms by one day or more in 41 (35%) of episodes. There was no significant difference in time between the onset of the episode and specimen collection between those with and without viruses detected (median 2 (1-4) and 2 (1-5.3) days respectively, P=0.42). Specimens were collected within four days after the onset of an episode in 221/276 (80%) cases.

VIRAL DETECTION

Viruses were detected in 226 of 292 reported episodes (77%); in 14 (4.8%) two viruses were detected, and in one three viruses were detected (fig 1). Picornaviruses were detected in 147 episodes, coronaviruses in 38, influenza and parainfluenza viruses each in 21, and respiratory syncytial virus in 12 (table II). Of the picornaviruses detected, 84 were rhinoviruses, and one had characteristics of both enterovirus and rhinovirus and has not been finally classified. The remaining 62 could not be cultured but are likely to be rhinoviruses, as most enteroviruses culture easily.

TABLE II--Viruses detected during reported respiratory episodes
----------------------------------------------------------------------------------------------------
                                              Method of detection
----------------------------------------------------------------------------------------------------
                            Polymerase                                      Antibody
                              chain                                          rise by
Virus                        reaction     Culture     Immunofluorescence     ELISA       Total
----------------------------------------------------------------------------------------------------
Rhinovirus/enterovirus         146          47                                            147*
Coronavirus                     17          14                                 21          38
Influenza viruses                           14               10                20          21
Parainfluenza
  Viruses 1, 2, and 3                        6                6                18          21
Respiratory syncytial virus                  6                6                12          12
Other                                        2                1                 2           3
----------------------------------------------------------------------------------------------------
*84 found to be rhinovirus on further testing; remainder were unidentified picornaviruses.
ELISA=enzyme linked immunosorbent assay.

Viruses were detected in 161 (81%) reported episodes of lower respiratory tract infection and 125 (80%) reported falls in peak expiratory flow. For episodes with respiratory tract symptoms or falls in peak flow, or with both, viral infections were detected in 80-85% (table III). The highest detection rate was in reported episodes of wheeze, cough, and upper respiratory tract symptoms together with a fall in peak expiratory flow. Presence of a virus did not significantly affect the duration or severity of reported episodes of lower respiratory tract symptoms or falls in peak expiratory flow.

TABLE III--Rate of detection of viruses according to number and type
of reported episodes of respiratory symptoms and fall in peak expiratory
flow
--------------------------------------------------------------------------------
                                                                No (%) with
                                                 No of             virus
Characteristics of episode                      episodes         detected
--------------------------------------------------------------------------------
Lower respiratory tract                           200            162 (81)
Peak flow fall                                    157            126 (80)
Lower respiratory tract and peak flow             130            105 (81)
Peak flow and upper respiratory tract             141            116 (82)
Lower and upper respiratory tract                 184            155 (84)
Cough                                             192            156 (81)
Cough and peak flow                               126            102 (81)
Cough and upper respiratory tract                 177            145 (82)
Cough, peak flow, and upper respiratory tract     113             94 (83)
Wheeze                                             82             66 (80)
Wheeze and peak flow                               58             48 (83)
Wheeze and upper respiratory tract                 73             61 (84)
Wheeze, peak flow, and upper respiratory tract     51             43 (84)
Wheeze, cough, peak flow, and upper
 respiratory tract                                 48             41 (85)

The samples from asymptomatic children were analysed by polymerase chain reaction for only picornavirus. The number of samples giving positive signals (8 (12%)) was significantly lower than that for samples from symptomatic children (P<0.001, McNemar's test). In five of the eight positive samples the signal was weak compared with that in samples from symptomatic children,²¹ and the three children whose samples gave a strong polymerase chain reaction signal all tested negative three weeks later.

PATTERNS OF ILLNESS

The median fall in peak expiratory flow for coronavirus infections was 56 (35-88) l/min, significantly less than the 85.5 (55-108) l/min observed for the other viruses (P=0.005). Similarly coronaviruses caused less severe lower respiratory tract symptoms than other viruses (median maximum lower respiratory symptom scores 3 (2-5) and 5 (3-7) respectively, P<0.05). No other significant differences in the patterns of illness caused by the different viruses were observed, though the number of detections was too small to assess these patterns properly.

Discussion

We detected upper respiratory viral infections in 80-85% of exacerbations of asthma in school age children. Picornaviruses (mostly rhinoviruses) accounted for two thirds of the viral infections. Coronavirus was the next commonest but caused less severe asthma exacerbations than other respiratory viruses. Continuous monitoring identified many less severe episodes that were not reported to the investigators. These findings emphasise the importance of viral infections as a cause of lower respiratory tract morbidity in children.

The community setting and the intensive monitoring carried out by the children and their parents enabled early sampling, which probably increased our detection rate of viruses. Without the polymerase chain reaction, however, our virus detection rate would have been similar to that in previous studies--around 40%.⁴

ACCURACY OF DATA

Previous studies of upper respiratory infections have suggested that detection with cell cultures missed many infections.²⁰ These were thought to be mainly rhinoviruses or undiscovered agents, and our results suggest that most are indeed rhinoviruses or coronaviruses. Many of the samples that had initially been culture negative but had given positive results with the picornavirus polymerase chain reaction later grew rhinoviruses on repeat culture for longer periods (several of these rhinoviruses were slow growing).²¹ The detection rate in samples from asymptomatic children and that of multiple pathogens in the same sample agreed with previous data.⁴ The seasonal distribution of viral detections was similar to that in previous studies (data not shown here). A semiquantitative analysis of the positive signals in the picornavirus positive polymerase chain reaction^{21 29} showed that the signal increased with the duration of upper respiratory symptoms (Kruskal-Wallis one way analysis of variance, P<0.05) and correlated with the severity of peak expiratory flow reductions (Spearman's rank correlation r=0.29, P<0.01).^{21 28} These observations suggest that our results are valid, as do the findings of Nicholson et al in adults.²⁹ Their study had lower detection rates but used less intensive surveillance and detection methods and took nasal and throat swabs instead of nasal aspirates.

A weakness of this study is the absence of a control group. We thought that asymptomatic children would be difficult to recruit to an intensive and invasive study of this type and that they would not constitute a valid control group since they would have less commitment to the study than symptomatic children. We did, however, take control samples when children were asymptomatic. These samples represent the best controls for non-specific properties of the mucus and other factors known to be important in viral infections such as family structure and socioeconomic status. However, they do not control for seasonal variation.¹⁶

ASSOCIATION WITH ASTHMA

Many of the respiratory episodes recorded by children were severe, with a median maximal fall in peak expiratory flow of over 50 l/min for all episodes identified and over 80 l/min for the reported episodes. The similarity of the seasonal patterns of the reported and unreported episodes suggests a common cause. Inspection of the charts for each child showed that most had relatively stable baseline peak expiratory flow recordings, with sudden severe falls associated with viral infections, followed by recovery to baseline again over the next two to three weeks (fig 1). Such episodic symptoms fit the syndrome previously described as "wheezy bronchitis."^{30 31} Further longitudinal study of this cohort will show whether such children will grow out of their asthma.

In conclusion, this study has shown that upper respiratory, principally rhinoviral infections are associated with 80-85% of reported exacerbations of asthma in a cohort of school age children. These findings have considerable implications for understanding the cause of recurrent wheezing in childhood.

We thank the children and their parents who contributed to this study, Morag Forsyth for help with the virus culture and diagnosis, and Jo Clough for help with planning the study and preparing the manuscript and recruiting the original cohort.

The study was supported by grants from Miles, New Haven, CT; Action Research; the National Asthma Campaign; the British Lung Foundation; the British Medical Association; and the Chest Heart and Stroke Association. Clement Clarke International and Allen and Hanburys shared the costs of the peak flow meters. SLJ received the 1990 British Medical Association H C Roscoe Fellowship, PKP was supported by the Medical Research Council of New Zealand, the Asthma Foundation of New Zealand, and Allen and Hanburys (NZ).

1. Picado C. Barcelona's asthma epidemics: clinical aspects and intriguing findings. Thorax 1992;47:197-200. [Medline]
2. Potter PC, Weinberg E, Shore SCL. Acute severe asthma: a prospective study of the precipitating factors in 40 children. S Afr Med J 1984;66:397-402. [Medline]
3. Carlsen KH, Orstavik I, Leegaard J, Hoeg H. Respiratory virus infections and aeroallergens and acute bronchial asthma. Arch Dis Child 1984;59:310-5. [Abstract]
4. Pattemore PK, Johnston SL, Bardin PG. Viruses as precipitants of asthma symptoms. I. Epidemiology. Clin Exp Allergy 1992;22:325-36. [Medline]
5. Horn MEC, Brain EA, Gregg I, Inglis JM, Yealland SJ, Taylor P. Respiratory viral infection and wheezy bronchitis in childhood. Thorax 1979;34:23-8. [Abstract]
6. Mitchell I, Inglis JM, Simpson H. Viral infection as a precipitant of wheeze in children: combined home and hospital study. Arch Dis Child 1978;53:106-11. [Abstract]
7. Hudgel DW, Langston L, Selner JC, McIntosh K. Viral and bacterial infections in adults with chronic asthma. Am Rev Respir Dis 1979;120:393-7. [Medline]
8. Jennings LC, Barns G, Dawson KP. The association of viruses with acute asthma. NZ Med J 1987;100:488-90.
9. McIntosh K, Ellis EF, Hoffman LS, Lybass TG, Eller JJ, Fulginiti VA. The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J Pediatr 1973;82:578-90. [Medline]
10. Henderson FW, Clyde WA, Collier AM, Denny FW, Senior RJ, Sheaffer CI, et al. The etiological and epidemiologic spectrum of bronchiolitis in pediatric practice. J Pediatr 1979;95:183-90. [Medline]
11. Horn MEC, Brain E, Gregg I, Yealland SJ, Taylor P. Respiratory viral infection in children: a survey in general practice, Roehampton 1967. J Hyg (Camb) 1975;74:157-68.
12. Minor TE, Dick EC, DeMeo AN, Ouellette JJ, Cohen M, Reed CE. Viruses as precipitants of asthmatic attacks in children. JAMA 1974;227:292-8. [Medline]
13. Roldaan AC, Masural N. Viral respiratory infections in asthmatic children staying in a mountain resort. Eur J Respir Dis 1982;63:140-50. [Medline]
14. Horn MEC, Reed SE, Taylor P. Role of viruses and bacteria in acute wheezy bronchitis in childhood: a study of sputum. Arch Dis Child 1979;54:587-92. [Abstract]
15. Mertsola J, Ziegler T, Ruuskanen O, Vanto T, Koivikko A, Halonen P. Recurrent wheezy bronchitis and viral respiratory infections. Arch Dis Child 1991;66:124-9. [Abstract]
16. Storr J, Lenney W. School holidays and admissions with asthma. Arch Dis Child 1989;64:103-7. [Abstract]
17. Beasley R, Coleman ED, Hermon Y, Holst PE, O'Donnell TV, Tobias M. Viral respiratory tract infection and exacerbations of asthma in adult patients. Thorax 1988;43:679-83. [Abstract]
18. Mitchell I, Inglis H, Simpson H. Viral infections in wheezy bronchitis and asthma in children. Arch Dis Child 1976;51:707-11. [Abstract]
19. Gwaltney JM Jr. The common cold. In: Mandell GL, Douglas RG Jr, Bennet JE, eds. Principles and practice of infectious diseases. New York: John Wiley, 1979:429-35.
20. Larson HE, Reed SE, Tyrrell DAJ. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 1980;5:221-9. [Medline]
21. Johnston SL, Sanderson G, Pattemore PK, Bardin PG, Bruce CB, Lambden PR, et al. Use of polymerase chain reaction for diagnosis of picornavirus infection in subjects with and without respiratory symptoms. J Clin Microbiol 1993;31:111-7. [Abstract/Free Full Text]
22. Myint S, Johnston S, Sanderson G, Simpson H. Evaluation of nested polymerase chain methods for the detection of human coronaviruses 229E and OC43. Molecular and Cellular Probes 1994;8:357-64. [Medline]
23. Clough JB, Williams JD, Holgate ST. Effect of atopy on the natural history of symptoms, peak expiratory flow, and bronchial responsiveness in 7- and 8-year old children with cough and wheeze. Am Rev Respir Dis 1991;143:755-60. [Medline]
24. Philpotts RJ. Clones of MRC-C cells may be superior to the parent line for the culture of 229E-like strains of human respiratory coronavirus. J Virol Methods 1983;6:267-9. [Medline]
25. Hamparian VV. Rhinoviruses. In: Lennette EH, Schmidt NJ, eds. Diagnostic procedures for viral, rickettsial and chlamydial infections. Washington, DC: American Public Health Association, 1979:562.
26. Schmidt NJ. Cell culture techniques for diagnostic virology. In: Lennette EH, Schmidt NJ, eds. Diagnostic procedures for viral, rickettsial and chlamydial infections. Washington, DC: American Public Health Association, 1979:67-9.
27. Kraaijeveld CA, Reed SE, Macnaughton MR. Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus 229E. J Clin Microbiol 1980;12:493-7. [Abstract/Free Full Text]
28. Johnston SL. The role of respiratory viral infections in exacerbations of asthma. [PhD thesis.] Southampton: University of Southampton, 1993:99-110,
29. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ 1993;307:982-6.
30. Clough JB, Holgate ST. Episodes of respiratory morbidity in children with cough and wheeze. American Journal of Respiratory Critical Care Medicine 1994;150:48-53. [Abstract]
31. Wilson NM. Wheezy bronchitis revisited. Arch Dis Child 1989;64:1194-9. [Medline]

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• Wiehler, S., Proud, D. (2007). Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L505-L515 [Abstract] [Full text]  
• Kato, A., Favoreto, S. Jr., Avila, P. C., Schleimer, R. P. (2007). TLR3- and Th2 Cytokine-Dependent Production of Thymic Stromal Lymphopoietin in Human Airway Epithelial Cells. J. Immunol. 179: 1080-1087 [Abstract] [Full text]  
• Johnston, S. L. (2007). Innate Immunity in the Pathogenesis of Virus-induced Asthma Exacerbations. Proc Am Thorac Soc 4: 267-270 [Abstract] [Full text]  
• Panitch, H. B. (2007). The Relationship Between Early Respiratory Viral Infections and Subsequent Wheezing and Asthma. CLIN PEDIATR 46: 392-400  
• Edwards, M. R., Haas, J., Panettieri, R. A. Jr., Johnson, M., Johnston, S. L. (2007). Corticosteroids and beta2 Agonists Differentially Regulate Rhinovirus-induced Interleukin-6 via Distinct Cis-acting Elements. J. Biol. Chem. 282: 15366-15375 [Abstract] [Full text]  
• McCann, K. L., Imani, F. (2007). Transforming Growth Factor {beta} Enhances Respiratory Syncytial Virus Replication and Tumor Necrosis Factor Alpha Induction in Human Epithelial Cells. J. Virol. 81: 2880-2886 [Abstract] [Full text]  
• Robertson, C. F., Price, D., Henry, R., Mellis, C., Glasgow, N., Fitzgerald, D., Lee, A. J., Turner, J., Sant, M. (2007). Short-Course Montelukast for Intermittent Asthma in Children: A Randomized Controlled Trial. Am. J. Respir. Crit. Care Med. 175: 323-329 [Abstract] [Full text]  
• Bentley, J. K., Newcomb, D. C., Goldsmith, A. M., Jia, Y., Sajjan, U. S., Hershenson, M. B. (2007). Rhinovirus Activates Interleukin-8 Expression via a Src/p110{beta} Phosphatidylinositol 3-Kinase/Akt Pathway in Human Airway Epithelial Cells. J. Virol. 81: 1186-1194 [Abstract] [Full text]  
• Nisar, N., Guleria, R., Kumar, S., Chand Chawla, T., Ranjan Biswas, N. (2007). Mycoplasma pneumoniae and its role in asthma. Postgrad. Med. J. 83: 100-104 [Abstract] [Full text]  
• Niimi, K., Asano, K., Shiraishi, Y., Nakajima, T., Wakaki, M., Kagyo, J., Takihara, T., Suzuki, Y., Fukunaga, K., Shiomi, T., Oguma, T., Sayama, K., Yamaguchi, K., Natori, Y., Matsumoto, M., Seya, T., Yamaya, M., Ishizaka, A. (2007). TLR3-Mediated Synthesis and Release of Eotaxin-1/CCL11 from Human Bronchial Smooth Muscle Cells Stimulated with Double-Stranded RNA. J. Immunol. 178: 489-495 [Abstract] [Full text]  
• Hershenson, M. B., Johnston, S. L. (2006). Rhinovirus Infections: More Than a Common Cold. Am. J. Respir. Crit. Care Med. 174: 1284-1285 [Full text]  
• Wang, X., Lau, C., Wiehler, S., Pow, A., Mazzulli, T., Gutierrez, C., Proud, D., Chow, C.-W. (2006). Syk Is Downstream of Intercellular Adhesion Molecule-1 and Mediates Human Rhinovirus Activation of p38 MAPK in Airway Epithelial Cells. J. Immunol. 177: 6859-6870 [Abstract] [Full text]  
• Proud, D., Chow, C.-W. (2006). Role of Viral Infections in Asthma and Chronic Obstructive Pulmonary Disease. Am. J. Respir. Cell Mol. Bio. 35: 513-518 [Abstract] [Full text]  
• Wang, H., Peters, N., Schwarze, J. (2006). Plasmacytoid Dendritic Cells Limit Viral Replication, Pulmonary Inflammation, and Airway Hyperresponsiveness in Respiratory Syncytial Virus Infection. J. Immunol. 177: 6263-6270 [Abstract] [Full text]  
• Mallia, P., Johnston, S. L. (2006). How viral infections cause exacerbation of airway diseases.. Chest 130: 1203-1210 [Abstract] [Full text]  
• Wark, P A B, Gibson, P G (2006). Asthma exacerbations {middle dot} 3: Pathogenesis.. Thorax 61: 909-915 [Abstract] [Full text]  
• Atkinson, R W, Strachan, D P, Anderson, H R, Hajat, S, Emberlin, J (2006). Temporal associations between daily counts of fungal spores and asthma exacerbations. Occup. Environ. Med. 63: 580-590 [Abstract] [Full text]  
• Singh, A M, Busse, W W (2006). Asthma exacerbations {middle dot} 2: Aetiology.. Thorax 61: 809-816 [Abstract] [Full text]  
• Culley, F. J., Pennycook, A. M. J., Tregoning, J. S., Dodd, J. S., Walzl, G., Wells, T. N., Hussell, T., Openshaw, P. J. M. (2006). Role of CCL5 (RANTES) in Viral Lung Disease.. J. Virol. 80: 8151-8157 [Abstract] [Full text]  
• Laza-Stanca, V., Stanciu, L. A., Message, S. D., Edwards, M. R., Gern, J. E., Johnston, S. L. (2006). Rhinovirus Replication in Human Macrophages Induces NF-{kappa}B-Dependent Tumor Necrosis Factor Alpha Production.. J. Virol. 80: 8248-8258 [Abstract] [Full text]  
• Oliveri, C, Polosa, R, Holgate, S T, Haworth, P H, Babu, K S, Arshad, H S (2006). Etanercept in chronic severe asthma * Authors' reply.. Thorax 61: 640-640 [Full text]  
• Harju, T H, Leinonen, M, Nokso-Koivisto, J, Korhonen, T, Raty, R, He, Q, Hovi, T, Mertsola, J, Bloigu, A, Rytila, P, Saikku, P (2006). Pathogenic bacteria and viruses in induced sputum or pharyngeal secretions of adults with stable asthma. Thorax 61: 579-584 [Abstract] [Full text]  
• Kozyrskyj, A. L., Dahl, M. E., Ungar, W. J., Becker, A. B., Law, B. J. (2006). Antibiotic treatment of wheezing in children with asthma: what is the practice?. Pediatrics 117: e1104-e1110 [Abstract] [Full text]  
• Peng, T., Kotla, S., Bumgarner, R. E., Gustin, K. E. (2006). Human rhinovirus attenuates the type I interferon response by disrupting activation of interferon regulatory factor 3.. J. Virol. 80: 5021-5031 [Abstract] [Full text]  
• Edwards, M. R., Johnson, M. W., Johnston, S. L. (2006). Combination Therapy: Synergistic Suppression of Virus-Induced Chemokines in Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 34: 616-624 [Abstract] [Full text]  
• Murray, C S, Poletti, G, Kebadze, T, Morris, J, Woodcock, A, Johnston, S L, Custovic, A (2006). Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61: 376-382 [Abstract] [Full text]  
• Teach, S. J., Crain, E. F., Quint, D. M., Hylan, M. L., Joseph, J. G. (2006). Indoor Environmental Exposures Among Children With Asthma Seen in an Urban Emergency Department.. Pediatrics 117: S152-S158 [Abstract] [Full text]  
• Chen, Y., Hamati, E., Lee, P.-K., Lee, W.-M., Wachi, S., Schnurr, D., Yagi, S., Dolganov, G., Boushey, H., Avila, P., Wu, R. (2006). Rhinovirus Induces Airway Epithelial Gene Expression through Double-Stranded RNA and IFN-Dependent Pathways. Am. J. Respir. Cell Mol. Bio. 34: 192-203 [Abstract] [Full text]  
• Creer, D D, Dilworth, J P, Gillespie, S H, Johnston, A R, Johnston, S L, Ling, C, Patel, S, Sanderson, G, Wallace, P G, McHugh, T D (2006). Aetiological role of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care. Thorax 61: 75-79 [Abstract] [Full text]  
• Chang, A. B., Glomb, W. B. (2006). Guidelines for Evaluating Chronic Cough in Pediatrics: ACCP Evidence-Based Clinical Practice Guidelines. Chest 129: 260S-283S [Abstract] [Full text]  
• Johnston, S. L. (2005). Impact of viruses on airway diseases. ERR 14: 57-61 [Abstract] [Full text]  
• Krenn, B. M., Holzer, B., Gaudernak, E., Triendl, A., van Kuppeveld, F. J., Seipelt, J. (2005). Inhibition of Polyprotein Processing and RNA Replication of Human Rhinovirus by Pyrrolidine Dithiocarbamate Involves Metal Ions. J. Virol. 79: 13892-13899 [Abstract] [Full text]  
• Newcomb, D. C., Sajjan, U., Nanua, S., Jia, Y., Goldsmith, A. M., Bentley, J. K., Hershenson, M. B. (2005). Phosphatidylinositol 3-Kinase Is Required for Rhinovirus-induced Airway Epithelial Cell Interleukin-8 Expression. J. Biol. Chem. 280: 36952-36961 [Abstract] [Full text]  
• Tsuji, K., Yamamoto, S., Ou, W., Nishi, N., Kobayashi, I., Zaitsu, M., Muro, E., Sadakane, Y., Ichimaru, T., Hamasaki, Y. (2005). dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells. Eur Respir J 26: 795-803 [Abstract] [Full text]  
• ten Brinke, A., Sterk, P. J., Masclee, A. A. M., Spinhoven, P., Schmidt, J. T., Zwinderman, A. H., Rabe, K. F., Bel, E. H. (2005). Risk factors of frequent exacerbations in difficult-to-treat asthma. Eur Respir J 26: 812-818 [Abstract] [Full text]  
• Pevear, D. C., Hayden, F. G., Demenczuk, T. M., Barone, L. R., McKinlay, M. A., Collett, M. S. (2005). Relationship of Pleconaril Susceptibility and Clinical Outcomes in Treatment of Common Colds Caused by Rhinoviruses. Antimicrob. Agents Chemother. 49: 4492-4499 [Abstract] [Full text]  
• Belmonte, K. E. (2005). Cholinergic Pathways in the Lungs and Anticholinergic Therapy for Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 2: 297-304 [Abstract] [Full text]  
• Johnston, S. L., Martin, R. J. (2005). Chlamydophila pneumoniae and Mycoplasma pneumoniae: A Role in Asthma Pathogenesis?. Am. J. Respir. Crit. Care Med. 172: 1078-1089 [Abstract] [Full text]  
• Holgate, S. T. (2005). Exacerbations: The Asthma Paradox. Am. J. Respir. Crit. Care Med. 172: 941-943 [Full text]  
• Xatzipsalti, M., Kyrana, S., Tsolia, M., Psarras, S., Bossios, A., Laza-Stanca, V., Johnston, S. L., Papadopoulos, N. G. (2005). Rhinovirus Viremia in Children with Respiratory Infections. Am. J. Respir. Crit. Care Med. 172: 1037-1040 [Abstract] [Full text]  
• Hewson, C. A., Jardine, A., Edwards, M. R., Laza-Stanca, V., Johnston, S. L. (2005). Toll-Like Receptor 3 Is Induced by and Mediates Antiviral Activity against Rhinovirus Infection of Human Bronchial Epithelial Cells. J. Virol. 79: 12273-12279 [Abstract] [Full text]  
• (2005). Pharmacotherapy -- treatment of intermittent asthma with ICSs. CMAJ 173: S33-S36 [Full text]  
• Frei, J., Jutla, J., Kramer, G., Hatzakis, G. E., Ducharme, F. M., Davis, G. M. (2005). Impulse Oscillometry: Reference Values in Children 100 to 150 cm in Height and 3 to 10 Years of Age. Chest 128: 1266-1273 [Abstract] [Full text]  
• Silverman, R. A., Ito, K., Stevenson, L., Hastings, H. M. (2005). The Relationship of Fall School Opening and Emergency Department Asthma Visits in a Large Metropolitan Area. Arch Pediatr Adolesc Med 159: 818-823 [Abstract] [Full text]  
• Busse, W. W., Gern, J. E. (2005). Is Interleukin-10 a "10" in Virus-provoked Asthma?. Am. J. Respir. Crit. Care Med. 172: 405-406 [Full text]  
• Grissell, T. V., Powell, H., Shafren, D. R., Boyle, M. J., Hensley, M. J., Jones, P. D., Whitehead, B. F., Gibson, P. G. (2005). Interleukin-10 Gene Expression in Acute Virus-induced Asthma. Am. J. Respir. Crit. Care Med. 172: 433-439 [Abstract] [Full text]  
• Peebles, R. S. Jr., Graham, B. S. (2005). Pathogenesis of Respiratory Syncytial Virus Infection in the Murine Model. Proc Am Thorac Soc 2: 110-115 [Abstract] [Full text]  
• Johnston, S. L. (2005). Overview of Virus-induced Airway Disease. Proc Am Thorac Soc 2: 150-156 [Abstract] [Full text]  
• O'Sullivan, S. M. (2005). Asthma Death, CD8+ T Cells, and Viruses. Proc Am Thorac Soc 2: 162-165 [Abstract] [Full text]  
• Holgate, S T, Lack, G (2005). Improving the management of atopic disease. Arch. Dis. Child. 90: 826-831 [Abstract] [Full text]  
• Turner, R. B., Bauer, R., Woelkart, K., Hulsey, T. C., Gangemi, J. D. (2005). An Evaluation of Echinacea angustifolia in Experimental Rhinovirus Infections. NEJM 353: 341-348 [Abstract] [Full text]  
• Fleming, D. M., Monto, A. S. (2005). Influenza Vaccination in Children with Asthma: No Reason to Change Current Recommendations. Am. J. Respir. Crit. Care Med. 171: 931-931 [Full text]  
• Wark, P. A.B., Johnston, S. L., Bucchieri, F., Powell, R., Puddicombe, S., Laza-Stanca, V., Holgate, S. T., Davies, D. E. (2005). Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J. Exp. Med. 201: 937-947 [Abstract] [Full text]  
• Mosser, A. G., Vrtis, R., Burchell, L., Lee, W.-M., Dick, C. R., Weisshaar, E., Bock, D., Swenson, C. A., Cornwell, R. D., Meyer, K. C., Jarjour, N. N., Busse, W. W., Gern, J. E. (2005). Quantitative and Qualitative Analysis of Rhinovirus Infection in Bronchial Tissues. Am. J. Respir. Crit. Care Med. 171: 645-651 [Abstract] [Full text]  
• Jokela, P., Joki-Korpela, P., Maaronen, M., Glumoff, V., Hyypia, T. (2005). Detection of Human Picornaviruses by Multiplex Reverse Transcription-PCR and Liquid Hybridization. J. Clin. Microbiol. 43: 1239-1245 [Abstract] [Full text]  
• Fonseca-Aten, M., Rios, A. M., Mejias, A., Chavez-Bueno, S., Katz, K., Gomez, A. M., McCracken, G. H. Jr., Hardy, R. D. (2005). Mycoplasma pneumoniae Induces Host-Dependent Pulmonary Inflammation and Airway Obstruction in Mice. Am. J. Respir. Cell Mol. Bio. 32: 201-210 [Abstract] [Full text]  
• Bisgaard, H., Zielen, S., Garcia-Garcia, M. L., Johnston, S. L., Gilles, L., Menten, J., Tozzi, C. A., Polos, P. (2005). Montelukast Reduces Asthma Exacerbations in 2- to 5-Year-Old Children with Intermittent Asthma. Am. J. Respir. Crit. Care Med. 171: 315-322 [Abstract] [Full text]  
• Reddel, H K, Vincent, S D, Civitico, J (2005). The need for standardisation of peak flow charts. Thorax 60: 164-167 [Abstract] [Full text]  
• Bueving, H.J., van der Wouden, J.C., Raat, H., Bernsen, R.M.D., de Jongste, J.C., van Suijlekom-Smit, L.W.A., Osterhaus, A.D.M.E., Rimmelzwaan, G.F., Molken, M. R.-v., Thomas, S. (2004). Influenza vaccination in asthmatic children: effects on quality of life and symptoms. Eur Respir J 24: 925-931 [Abstract] [Full text]  
• Gruteke, P., Glas, A. S., Dierdorp, M., Vreede, W. B., Pilon, J.-W., Bruisten, S. M. (2004). Practical Implementation of a Multiplex PCR for Acute Respiratory Tract Infections in Children. J. Clin. Microbiol. 42: 5596-5603 [Abstract] [Full text]  
• Garbino, J., Gerbase, M. W., Wunderli, W., Deffernez, C., Thomas, Y., Rochat, T., Ninet, B., Schrenzel, J., Yerly, S., Perrin, L., Soccal, P. M., Nicod, L., Kaiser, L. (2004). Lower Respiratory Viral Illnesses: Improved Diagnosis by Molecular Methods and Clinical Impact. Am. J. Respir. Crit. Care Med. 170: 1197-1203 [Abstract] [Full text]  
• Biscione, G.L., Corne, J., Chauhan, A.J., Johnston, S.L. (2004). Increased frequency of detection of Chlamydophila pneumoniae in asthma. Eur Respir J 24: 745-749 [Abstract] [Full text]  
• Yamamoto, S., Kobayashi, I., Tsuji, K., Nishi, N., Muro, E., Miyazaki, M., Zaitsu, M., Inada, S., Ichimaru, T., Hamasaki, Y. (2004). Upregulation of Interleukin-4 Receptor by Interferon-{gamma}: Enhanced Interleukin-4-Induced Eotaxin-3 Production in Airway Epithelium. Am. J. Respir. Cell Mol. Bio. 31: 456-462 [Abstract] [Full text]  
• Sha, Q., Truong-Tran, A. Q., Plitt, J. R., Beck, L. A., Schleimer, R. P. (2004). Activation of Airway Epithelial Cells by Toll-Like Receptor Agonists. Am. J. Respir. Cell Mol. Bio. 31: 358-364 [Abstract] [Full text]  
• Hashimoto, K., Graham, B. S., Ho, S. B., Adler, K. B., Collins, R. D., Olson, S. J., Zhou, W., Suzutani, T., Jones, P. W., Goleniewska, K., O'Neal, J. F., Peebles, R. S. Jr. (2004). Respiratory Syncytial Virus in Allergic Lung Inflammation Increases Muc5ac and Gob-5. Am. J. Respir. Crit. Care Med. 170: 306-312 [Abstract] [Full text]  
• Turner, R. B., Biedermann, K. A., Morgan, J. M., Keswick, B., Ertel, K. D., Barker, M. F. (2004). Efficacy of Organic Acids in Hand Cleansers for Prevention of Rhinovirus Infections. Antimicrob. Agents Chemother. 48: 2595-2598 [Abstract] [Full text]  
• Busse, W W, Lemanske, R F Jr (2004). Management of asthma exacerbations. Thorax 59: 545-546 [Full text]  
• FitzGerald, J M, Becker, A, Sears, M R, Mink, S, Chung, K, Lee, J (2004). Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 59: 550-556 [Abstract] [Full text]  
• Bont, L, Steijn, M, van Aalderen, W M C, Brus, F, Th Draaisma, J M, Van Diemen-Steenvoorde, R A A M, Pekelharing-Berghuis, M, Kimpen, J L L (2004). Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection. Thorax 59: 512-516 [Abstract] [Full text]  
• Lee, A. M., Fryer, A. D., van Rooijen, N., Jacoby, D. B. (2004). Role of macrophages in virus-induced airway hyperresponsiveness and neuronal M2 muscarinic receptor dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L1255-L1259 [Abstract] [Full text]  
• Foliaki, S., Nielsen, S. K., Bjorksten, B., von Mutius, E., Cheng, S., Pearce, N., the ISAAC Phase I Study Group, (2004). Antibiotic sales and the prevalence of symptoms of asthma, rhinitis, and eczema: The International Study of Asthma and Allergies in Childhood (ISAAC). Int J Epidemiol 33: 558-563 [Abstract] [Full text]  
• Pekkanen, J. (2004). Commentary: Use of antibiotics and risk of asthma. Int J Epidemiol 33: 564-565 [Full text]  
• Pauwels, R. A. (2004). Similarities and Differences in Asthma and Chronic Obstructive Pulmonary Disease Exacerbations. Proc Am Thorac Soc 1: 73-76 [Abstract] [Full text]  
• Holgate, S. T., Holloway, J., Wilson, S., Bucchieri, F., Puddicombe, S., Davies, D. E. (2004). Epithelial-Mesenchymal Communication in the Pathogenesis of Chronic Asthma. Proc Am Thorac Soc 1: 93-98 [Abstract] [Full text]  
• Murray, C. S., Simpson, A., Custovic, A. (2004). Allergens, Viruses, and Asthma Exacerbations. Proc Am Thorac Soc 1: 99-104 [Abstract] [Full text]  
• Wedzicha, J. A. (2004). Role of Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 1: 115-120 [Abstract] [Full text]  
• Proud, D., Sanders, S. P., Wiehler, S. (2004). Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human {beta}-Defensin 2 Both In Vitro and In Vivo. J. Immunol. 172: 4637-4645 [Abstract] [Full text]  
• WinklerPrins, V., van den Nieuwenhof, L., van den Hoogen, H., Bor, H., van Weel, C. (2004). The Natural History of Asthma in a Primary Care Cohort. Ann Fam Med 2: 110-115 [Abstract] [Full text]  
• Bueving, H. J., Bernsen, R. M. D., de Jongste, J. C., van Suijlekom-Smit, L. W. A., Rimmelzwaan, G. F., Osterhaus, A. D. M. E., Molken, M. P. M. H. R.-v., Thomas, S., van der Wouden, J. C. (2004). Influenza Vaccination in Children with Asthma: Randomized Double-Blind Placebo-controlled Trial. Am. J. Respir. Crit. Care Med. 169: 488-493 [Abstract] [Full text]  
• Message, S. D., Johnston, S. L. (2004). Host defense function of the airway epithelium in health and disease: clinical background. J. Leukoc. Biol. 75: 5-17 [Abstract] [Full text]  
• Hayden, F. G., Turner, R. B., Gwaltney, J. M., Chi-Burris, K., Gersten, M., Hsyu, P., Patick, A. K., Smith, G. J. III, Zalman, L. S. (2003). Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers. Antimicrob. Agents Chemother. 47: 3907-3916 [Abstract] [Full text]  
• Chauhan, A. J, Johnston, S. L (2003). Air pollution and infection in respiratory illness. Br Med Bull 68: 95-112 [Abstract] [Full text]  
• Johnston, S. L. (2003). Experimental Models of Rhinovirus-induced Exacerbations of Asthma: Where to Now?. Am. J. Respir. Crit. Care Med. 168: 1145-1146 [Full text]  
• de Kluijver, J., Evertse, C. E., Sont, J. K., Schrumpf, J. A., van Zeijl-van der Ham, C. J. G., Dick, C. R., Rabe, K. F., Hiemstra, P. S., Sterk, P. J. (2003). Are Rhinovirus-induced Airway Responses in Asthma Aggravated by Chronic Allergen Exposure?. Am. J. Respir. Crit. Care Med. 168: 1174-1180 [Abstract] [Full text]  
• Brooks, G. D., Buchta, K. A., Swenson, C. A., Gern, J. E., Busse, W. W. (2003). Rhinovirus-induced Interferon-{gamma} and Airway Responsiveness in Asthma. Am. J. Respir. Crit. Care Med. 168: 1091-1094 [Abstract] [Full text]  
• Tuthill, T. J., Papadopoulos, N. G., Jourdan, P., Challinor, L. J., Sharp, N. A., Plumpton, C., Shah, K., Barnard, S., Dash, L., Burnet, J., Killington, R. A., Rowlands, D. J., Clarke, N. J., Blair, E. D., Johnston, S. L. (2003). Mouse respiratory epithelial cells support efficient replication of human rhinovirus. J. Gen. Virol. 84: 2829-2836 [Abstract] [Full text]  
• Gern, J. E., Brockman-Schneider, R., Bhattacharya, S., Malter, J. S., Busse, W. W. (2003). Serum and Low-Density Lipoprotein Enhance Interleukin-8 Secretion by Airway Epithelial Cells. Am. J. Respir. Cell Mol. Bio. 29: 483-489 [Abstract] [Full text]