Enrollment included 112 subjects and 95 completed the study. During the year 9 subjects dropped out of the study due to ill health and 8 died. Of the subjects, 86 (77%) made all seven routine visits and 102 (91%) made four or more visits. Most subjects (97%) were under the care of a pulmonary specialist. Subjects had a mean of 54 pack-years of smoking history and 48% complained of chronic sputum production (). Many subjects used inhaled steroids (67%), chronic oral steroids (20%), or home oxygen (47%). For 65 subjects (58%) pulmonary function test results were available; in this subset the mean FEV1 was 44 ± 19% of predicted.
Overall, 685 routine evaluations were performed, yielding 685 nasal samples and 315 sputum samples for RT-PCR analysis. RSV RNA was detected in 0 of the 685 nasal and in 3 (0.9%) of the 315 sputum samples (). During the 12-mo follow-up period, 134 respiratory illnesses were reported, of which 92 (69%) were evaluated during the acute phase with the collection of 92 nasal and 69 sputum samples. Ill subjects were evaluated an average of 2.9 ± 1.6 d after onset of symptoms, and six nasal (6.5%) and five sputum (7.2%) samples were RT-PCR positive. The RSV detection rate in acute illness samples was significant greater than in routinely obtained nasal (p < 0.0001) and sputum samples (p = 0.006). Overall, 30% of the 384 sputum samples were judged to be adequate, 44% adequate but contaminated, and 26% inadequate.
RESPIRATORY SYNCYTIAL VIRUS REVERSE TRANSCRIPTASE–POLYMERASE CHAIN REACTION RESULTS
From RT-PCR and serology, 14 subjects showed evidence of RSV infections with 1 subject showing evidence of two infections () Seven infections were RT-PCR positive and associated with a greater-than-fourfold rise in serum or nasal antibody, three were RT-PCR positive only, and four were identified by serologic response only. Of the 15 RSV infections, 11 were identified during illness visits (subjects 1–10), including both infections in subject 1. The latter subject had two RT-PCR positive illnesses approximately 2 mo apart, the second one associated with seroconversion. Of the four RSV-infected subjects with clinically unrecognized infection, three were identified by a positive sputum RT-PCR collected on routine visits (subjects 12–14). Of these three, one had no symptoms, one complained of increased cough at the time of the visit, and the other complained of feeling unwell with increased dyspnea for 1 wk preceding the visit. However, neither of the latter two subjects perceived a “new respiratory illness” warranting an illness evaluation at the time of the positive RT-PCR sample collection. One of these subjects (subject 12) demonstrated a serologic response at the time of the positive RT-PCR.
SUMMARY OF RESPIRATORY SYNCYTIAL VIRUS–POSITIVE SUBJECTS
Quantitative RT-PCR was performed on all positive nasal and sputum samples and expressed as pfu/ml of sample (). The mean peak viral load by quantitative RT-PCR was 38,620 ± 64,750 pfu (range, 2–156,000) in illness samples and 82 ± 140 (range, 0.01–250) in routine samples. Due to the small numbers and the wide range of values, this difference was not statistically significant. The viral load of RSV RNA in nasal samples was lower than in sputum in almost all instances. In 9 of 11 nasal and sputum pairs collected simultaneously, the sputum viral load was higher than the nasal (p = 0.008, Mann-Whitney test). In addition, sputum samples remained positive longer than nasal samples (13.8 ± 7.6 vs. 10.1 ± 7.3 d) although this difference was not significant.
RESPIRATORY SYNCYTIAL VIRUS TITERS IN SYMPTOMATIC SUBJECTS
All RT-PCR positive samples were collected between October and May, with clear clustering in January (), and all were group B by strain-specific RT-PCR, including both illness samples from subject 1. Sequences of the 190 nucleotide amplified F gene segment from these two samples were both consistent with the B1 genotype, although they differed by 2 nucleotides at positions 713 A/G and 916 A/G.
Figure 1. Distribution of respiratory synctial virus (RSV) cases by month of identification. Cases associated with illness and reverse transcriptase–polymerase chain reaction (RT-PCR) positive nasal or sputum specimens are shown in black. Cases associated (more ...)
The subjects who were identified as RSV positive by RT-PCR or serology did not differ significantly from subjects who did not have RSV in age, sex, smoking status, pulmonary function, or steroid use (). The clinical characteristics of the 11 RSV illnesses are outlined in . Most subjects were moderately ill with complaints of increased cough (100%), sputum (45%), and dyspnea (73%). Only 1 of 11 had symptoms limited to the upper respiratory tract. At least one office visit was made by 73 % of the subjects and one subject was hospitalized for 3 d. On average, subjects were unable to perform their activities of daily living for 9 d. Evaluated by standards set forth by Anthonsien and colleagues for acute exacerbation of COPD, 91% of those with an identified illness met exacerbation criteria (25
RESPIRATORY SYNCYTIAL VIRUS ILLNESS CHARACTERISTICS
The subject who experienced two symptomatic RSV B infections was moderately ill with nasal congestion, cough, dyspnea, and wheezing lasting 3 to 4 wk during both episodes. The first illness occurred on December 31, 2004, with an evaluation 4 d later. Nasal RT-PCR was positive with a viral load of 247 pfu and sputum was unavailable. This episode was not associated with a serologic response. The second illness occurred on March 7, 2005, and she had repeatedly negative nasal specimens with positive sputum over a 2-wk period. The initial viral load in the sputum was 23,700, and this episode was associated with a eightfold rise in serum IgG and fourfold rise in nasal IgA RSV titers. Routine evaluations of both nasal and sputum specimens in April, June, and August 2005 were all negative. Throughout this period, she used nasal and inhaled corticosteroids as well as oral prednisone at 2 mg/d.