Details about Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity, and Quality of Life in a Cohort of Survivors

Of the first 138 patients with SARS infection in March 2003, 15 patients (10.9%) died. Among the 123 survivors, 13 patients (10.6%) did not attend follow-up at 3 months and 6 months, whereas another 13 patients (10.6%) defaulted the 12-month assessment. Of the 13 defaulters at 12 months, 11 patients had normal lung function indexes, whereas the other 2 patients had Dlco of 68% and 78% of predicted normal values, respectively, at 6 months. Thus, there were only 97 patients (78.9%) who had completed the three assessments; among these, 63 patients (65%) were HCWs (doctors, nurses, ward assistants, and medical students) and 58 patients (66%) were women. The mean age was 36.9 years (SD, 9.5 years) and body mass index (BMI) was 23.7 kg/m2 (SD, 4.0 kg/m2) during the visit at 12 months from illness onset. The hospital length of stay (LOS) for the group was 22.7 days (SD, 14.6 days). There were only three smokers (3.3%) among the whole group. There were 15 patients with medical comorbidities, which included COPD (n = 1; 1.1%); ischemic heart disease (n = 1; 1.1%); ischemic stroke (n = 1; 1.1%); breast cancer (patient in stable clinical condition receiving tamoxifen) [n = 1; 1.1%]; diabetes mellitus (n = 3; 3.3%); cirrhosis (n = 1; 1.1%), hypertension (n = 4; 4.1%); and asymptomatic hepatitis B carrier (n = 3; 3.3%).

Among the 97 patients, 31 patients (32%; 17 men and 14 women) required ICU admission, with an ICU LOS of 13.5 days (SD, 15.6 days; median, 7 days; range, 2 to 64 days), whereas 6 patients (5.5%) required invasive mechanical ventilation. Based on our ICU admission criteria, all 31 patients would have a Pa02/fraction of inspired oxygen ratio < 300 mm Hg, whereas the 6 patients who were intubated had a Pa02/fraction of inspired oxygen ratio < 200 mm Hg. Among these 31 patients, 6 patients had medical comorbidities, including ischemic heart disease (n = 1; 0.9%), diabetes mellitus (n = 1; 0.9%), hypertension (n = 2; 1.8%), and asymptomatic hepatitis B carrier (n = 2; 1.8%), but none had any history of smoking or pulmonary disease. Treat pulmonary diseases together with medications of Canadian Health&Care Mall.

Lung Function Tests and Respiratory Muscle Strength

An overview of the serial lung function tests and respiratory muscle strength results for the group are shown in Table 1. Overall, lung volume parameters and surface area for exchange were well preserved at 3, 6, and 12 months. There was significant reduction in Dlco, FEF25 75, and alveolar volume (Va), whereas there was an increase in Kco over the study period of 12 months. Plmax and PEmax values < 80 cm H2O were noted in 16 patients (14.5%) and 8 patients (7.3%), respectively, at 12 months.

The frequency of SARS survivors with lung function parameters < 80% of predicted values is as follows: 3 months, FEV1 (n = 3; 3.1%), FVC (n = 6; 6.2%), VC (n = 6; 6.2%), TLC (n = 7; 7.3%), Dlco (n = 13; 13.5%), and Kco (n = 2; 2.1%); 6 months, FEV1 (n = 4; 4.1%), FVC (n = 4; 4.1%), VC (n = 5; 5.2%), TLC (n = 8; 8.2%), Dlco (n = 15; 15.5%), and Kco (n = 1; 1.0%); and 12 months, FEVj (n = 5; 5.2%), FVC (n = 4; 4.1%), VC (n = 5; 5.2%), TLC (n = 5; 5.2%), Dlco (n = 23; 23.7%), and Kco (n = 0; 0%). Thus, there were 23 patients (23.7%) with impaired Dlco, whereas up to 5.2% of patients had reduction in parameters of lung volume at 12 months.

6MWD

The mean 6MWD increased significantly, from 464 m (SD, 87 m) at 3 months to 502 m (SD, 97 m) and 511 m (SD, 90 m) at 6 months and 12 months, respectively (p value for trend < 0.01). When the subjects were stratified into different age groups and compared to the corresponding normative values, their exercise capacity was generally significantly lower than the normal subjects (Table 2). The 6MWDs of the SARS survivors at 3, 6 and 12 months, in comparison with normative data, are shown in Table 3.

Determinants of 6MWD

Univariate followed by multivariate analyses, controlled for age and gender, were performed to look for factors associated with 6MWD (Table 3). At 3 months, there was no independent predictor identified, whereas percentage of predicted FVC was the only positive independent predictor for 6MWD at 6 months. At 12 months, the independent positive predictors for 6MWD were percentage of predicted FVC and percentage of predicted Dlco.

CXR and Correlations With Lung Function and 6MWD

Thirty-seven patients (38.1%) were noted to have abnormal total CXR scores at 3 months involving 3.9% (SD, 3.5%; range, 0.5 to 15%) of the total lung fields, whereas 32 patients (33%) had abnormal CXR scores involving 3.1% (SD, 3.4%; range, 0.8 to 15%) of the lung fields at 6 months. At 1 year, 27 patients (27.8%) had abnormal CXR findings involving 2.9% (SD, 3.1%; range, 0.8 to 15%) of lung fields. By repeated-measures ANOVA analysis of patients with abnormal CXR scores (n = 37), there was a significant trend for improvement from 3 to 12 months (p = 0.001).

Correlations between the extent of CXR abnormality vs cumulative steroid dosage, lung function parameters, and 6MWD at 12 months were examined. There was a significant positive correlation between the extent of radiographic abnormalities (percentage of lung fields) and the cumulative hydrocortisone dosage (r = 0.43, p < 0.01). There were significant negative correlations between the extent (percentage) of radiographic abnormalities and TLC (r = — 0.25, p = 0.01) and Dlco (r = — 0.37, p < 0.01). However, no significant correlations were noted between the extent of radiographic abnormalities vs 6MWD (r = — 0.14, p = 0.17), FEV1 (r =— 0.08, p = 0.42), RV (r = — 0.21, p = 0.05), FVC (r = — 0.19, p = 0.06), Kco (r = — 0.16, p = 0.11), Plmax (r =— 0.02, p = 0.88), and PEmax (r = 0.09, p = 0.41).

Comparison of Patients Who Required ICU Support vs Those Who Were Treated on the Medical Wards

Patients who had required ICU admission (n = 31; 17 men and 14 women) had a higher peak lactate dehydrogenase (LDH) level, a higher peak C-reactive protein (CRP) level, a longer hospital LOS, and received a significantly higher total steroid dose than those who did not require ICU care (Table 4). The lung function tests at 12 months showed significantly lower percentage of predicted FVC, VC, TLC, RV, and Dlco in survivors who required ICU support than those who were treated on medical wards, although no significant difference was noted for 6MWD and respiratory muscle strength between the two groups (Table 5).

Health Status Among SARS Survivors and Its Correlation With Lung Function Parameters

By repeated-measures ANOVA of the serial scores of the eight SF-36 domains for the entire cohort over 12 months, there were significant trends for mean improvement in RP of 37.6 (SD, 39.7), 61.1 (SD, 43.8), and 58.5 (SD, 43.0) at 3, 6, and 12 months, respectively [p for trend < 0.001]; SF of 63.4 (SD, 25.0), 72.4 (SD, 22.5), and 68.9 (SD, 25.1) at 3, 6, and 12 months, respectively [p for trend 0.001]; and RE of 51.6 (SD, 43.8), 68.4 (SD, 39.5), and 63.6 (SD, 42.8) at 3, 6, and 12 months, respectively [p for trend < 0.001], whereas there was worsening of GH: 53.4 (SD, 19.7), 51.5 (SD, 19.2), and 49.1 (SD, 19.1) at 3, 6, and 12 months, respectively (p for trend 0.023), There were no significant serial changes in PF, BP, VT, and MH (data not shown).

Correlations between lung function parameters, 6MWD, and SF-36 domains at 12 months are shown in Table 6. In general, there were significant positive correlations between lung function parameters (FVC, VC, FEV1, and Dlco) with several SF-36 domains (PF, RP, GH, SF, and RE). 6MWD had significant positive correlations with all SF-36 domains except MH.

SF-36 domain scores at 3, 6, and 12 months after illness onset in patients who did and did not require ICU support during the acute illness in comparison to normative data are shown in Figure 1 (more data are available only in on-line supplemental Tables 7-9). There was significant impairment of health status among our SARS survivors at 12 months compared to control subjects of the same age groups. People of all age may place an order fro drugs via Canadian Health&Care Mall.

When directly comparing those who had required ICU admission against those treated on the medical wards, there was no significant difference in all SF-36 domains between the two groups at 12 months. When comparing the 25 patients who did not require intubation in ICU against those who had required intubation (n = 6), the latter had more severe lung injury, as reflected by a higher peak LDH level: median, 466.0 U/L (interquartile range [IQR, 259.0 U/L]) vs 652.0 U/L (IQR, 124.5 U/L) [p = 0.02]. There was, however, no statistically significant difference with regard to age (36.0 years [IQR, 15.5 years] vs 36.5 years [IQR, 17.5 years], p = 0.87) and 6MWD (538.5.7 m [IQR, 170.2 m] vs 548.3 m [IQR, 118.1 m]; p = 0.71) at 12 months. In addition, there were no significant differences between the two groups with regard to lung function indexes and SF-36 domain scores at 12 months (data available only in on-line supplemental Table 10).

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Figure 1. HRQoL (SF-36) among SARS survivors at 3, 6, and 12 months after illness onset in comparison with HK normative data stratified into different age groups. The vertical axis represents SF-36 domain score in mean (SD) from 0 (minimum) to 100 (maximum), whereas the horizontal axis defines age groups in years. Based on the study by Lam et al, there were 1,244 normal subjects and 695 normal subjects in the age groups of 18 to 40 years and 41 to 64 years, respectively. There were 19 SARS survivors and 12 SARS survivors who had required ICU support in the age groups of 18 to 40 years and 41 to 64 years, whereas there were 60 SARS survivors and 19 SARS survivors who did not require ICU support in the same age groups, respectively. *Significant at p < 0.01. **Significant at p < 0.03. #Significant at p < 0.05. mth = month.
Table 1—Results of Serial Pulmonary Function Tests and Respiratory Muscle Strength Among SARS Survivors (n = 97)

Table 2—(>MWD Among SARS Survivors (n = 97) at 3, 6, and 12 Months After Illness Onset in Comparison With HK Normative Data

Table 3—Predictors of 6MWD at 3, 6, and 12 Months From Symptom Onset (n = 97)

Table 4—Comparison of Demographics, Biochemical Markers, and Steroid Dosage in SARS Survivors Who Required ICU Support vs Those Treated on Medical Wards

Table 5—Comparison of Lung Function Indexes, Respiratory Muscle Strength, and 6MWD in SARS Survivors Who Required ICU Care (n = 31) vs Those Treated on Medical Wards (n = 66)

Table 6—Correlations Among HRQoL, Pulmonary Function, and 6MWS at 12 Months (n = 97)

Table 7—Correlations of CXR Scores vs Steroid Dosage, 6MWD, and Lung Function Test Parameters at 12 Months (n = 97)

Table 8—HRQoL (SF-36) Among SARS Survivors (n = 31) Who Required ICU Admission, at 3, 6, and 12 Months After Illness Onset in Comparison With HK Normative Data Stratified Into Different Age Groups

Table 9—HRQoL (SF-36) Among SARS Survivors (n = 66) Who Did Not Require ICU Admission at 3, 6, and 12 Months After Illness Onset in Comparison With K Normative Data Stratified Into Different Age Groups

Table 10—Comparison of Age and LDH Levels During Hospitalization and Outcome at 12 Months Between Patients Who Required Invasive Ventilatory Support (n = 6) vs Those Not Requiring Intubation in the ICU (n = 25)