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

Severe lung injuryThis prospective cohort study has shown that 23.7% and 27.8% of SARS survivors had impairment of Dlco and abnormal CXR findings, respectively, at 1 year after illness onset. Overall, the serial assessments of 6MWD showed a significant improvement over 12 months, but exercise capacity and health status were still significantly lower than those of normal control subjects of the same age groups. The 1-year lung function indexes (percentage of predicted FVC, VC, TLC, RV, and Dlco) in survivors who required ICU support were remarkably lower than those of patients who were treated on medical wards, although no significant differences were noted for 6MWD, respiratory muscle strength, and health status between the two groups. Interestingly, there was no difference in lung function indexes, exercise capacity, and health status at 1 year between the ICU-intubated and the ICU-nonintu-bated SARS patients, although the former had more severe lung injury cured by Canadian Health&Care Mall.

Based on the HRCT appearance of bronchiolitis obliterans organizing pneumonia (BOOP) and the clinical suspicion that progression of the pulmonary disease might be mediated by the host inflammatory response, pulse methylprednisolone was administered during clinical progression of SARS with a favorable response. Lung histopathologic condition of fatal SARS cases was dominated by diffuse alveolar damage and extensive consolidation, but features of BOOP were indeed noted.

At 6 months after admission to hospital, residual abnormalities of pulmonary function were observed in three fourths of the Queen Elizabeth Hospital cohort in HK (n = 57), mostly consisting of isolated reductions in Dlco, whereas an abnormal HRCT score was detected in 75.4% of patients. In contrast, 15.5% of our SARS survivors had impaired Dlco at 6 months, whereas HRCT performed on 44 patients revealed ground-glass opacification and reticulation in 38 patients (86.4%) and 35 patients (92.1%), respectively. At 1 year, 23.7% of our patients had significant impairment of Dlco with well-preserved Kco. The serial results suggest an increase of the intra-alveolar diffusion pathway, which might be the result of diffuse alveolar damage and/or BOOP initially, followed by postinflam-matory changes such as atelectasis, ongoing alveolitis, and parenchymal fibrosis later in the course of the disease. Our results are similar to a long-term follow-up study in Beijing that reported that 27.3% of their SARS survivors (85 of 311 patients) had impaired Dlco, whereas 21.5% exhibited radiographic evidence of lung fibrotic changes at 1 year. Several studies on ARDS survivors have shown that their pulmonary function generally returns to normal or near normal by 6 to 12 months, but Dlco may remain abnormal in up to 80% of patients at 1 year after recovery. The decreasing trend for Va, discordant with TLC, observed in our study suggests there might be maldistribution of the inert gas during the single-breath Dlco maneuver, such as in the setting of occult small airway obstruction in some patients. Although expiratory HRCT was not performed in adult patients,, a pediatric study of 47 asymptomatic children at 6 months from diagnosis of SARS showed that 16 patients (34%) had pulmonary abnormalities, whereas 8 patients (17%) had evidence of air trapping on expiratory HRCT.

SARSThe self-paced 6MWT was performed to evaluate the global and integrated responses to exercise, although it did not provide specific information on the function of individual organs and systems improved due to medicines of Canadian Health&Care Mall.

Although showing considerable improvement over 12 months, the 6MWD was markedly reduced for most age groups compared to normal control subjects. Previous studies’ have shown that 6MWD was substantially lower among ARDS survivors than control subjects 1 to 2 years after mechanical ventilation, whereas the absence of systemic steroid treatment, absence of illness acquired during ICU stay, and rapid resolution of lung injury were important factors associated with a longer 6MWD at 3, 6, and 12 months, respectively. After controlling for the known effects of age and gender, our analysis has shown that percentage of predicted FVC was the positive independent factor associated with higher 6MWD at 6 months, whereas percentage of predicted FVC and percentage of predicted Dlco were the positive independent predictors at 12 months.

Given the relatively well-preserved lung function in the majority of our SARS survivors, the poor performance in the 6MWT in most age groups could be due to additional factors such as muscle wasting, myopathy, and possibly cardiac diastolic dysfunc-tion. Lau et al noted that muscle strength and endurance were more impaired in proximal than in distal muscles among survivors in our SARS cohort at 3 months after illness onset. Eighteen of 44 SARS survivors in Singapore had reduced exercise capacity at 3 months after hospital discharge that could not be accounted for by impairment of pulmonary func-tion. These results suggest that the inability to exercise in recovered SARS patients is primarily due to extrapulmonary causes such as physical deconditioning and possibly steroid myopathy.” In addition, 53% of SARS survivors complained of some degree of large-joint pain, although only 12 patients (4.7%, including 7 patients in the current study) of 254 SARS survivors in our cluster of hospitals had evidence of osteonecrosis of the long bones on MRI conducted at a median of 6.7 months from hospital admission.

There are several possible causes for muscle weakness among SARS survivors. More than 60% of our patients complained of myalgia with elevation of creatinine kinase in 32.1% suggestive of viral-induced myositis at initial presentation. Most of our patients required bed rest during hospitalization for an average of 3 weeks. The long period of bed rest could lead to muscle wasting and deconditioning, whereas the use of systemic corticosteroid therapy to suppress immune-mediated lung injury’’ could contribute to myopathy. Steroid myopathy has been reported in patients administered high-dose steroid for acute lung transplant rejection and status asth-maticus. Critical illness-associated polyneuropathy/ myopathy has also been observed in SARS survi-vors. A small proportion of our SARS patients had evidence of respiratory muscle weakness. Inspiratory muscle weakness may cause atelectasis, whereas expiratory muscle (abdominal and intercostal muscles) weakness may lead to air trapping.

ARDSIn addition, there was significant impairment of health status in most SF-36 domains among our patients at 12 months. There were significant and positive correlations between lung function parameters (VC, FVC, FEV1, and Dlco) and SF-36 domains such as PF, RP, GH, SF, and RE. There were also significant positive correlations between 6MWD and all SF-36 domains except for MH. The results are not surprising as, in addition to the physical impairment, the long period of isolation and extreme uncertainty during the SARS illness had created enormous psychological stress and mood disturbances. In addition, steroid toxicity, personal vulnerability, and psychosocial stressors might have jointly contributed to the development of psychosis in some patients. Other studies on acute lung injury or ARDS survivors unrelated to SARS have reported impaired health status at 1 to 5 years after recovery, whereas pulmonary function abnormalities, especially Dlco, correlated with SF-36 domains.

Twenty-seven patients (27.8%) in this study still had abnormal radiographic scores at 12 months, although their serial CXRs showed significant improvement. The positive correlation between the extent of residual radiographic abnormalities and the cumulative steroid dosage used for SARS was expected, as the former was an indication on the treatment protocol for more systemic steroid during the outbreak. The negative correlation between residual radiographic abnormality and lung volume parameter (TLC) and parameter of surface area for gas exchange (Dlco) reflected the physiologic effects of parenchymal inflammation and fibrosis. Patients with more severe disease (as reflected by higher peak LDH level)’’ who had required ICU support during the acute illness had more residual opacities on CXRs at 12 months. In addition, they had more extensive pulmonary injury and fibrosis, as reflected by a significantly lower lung volume parameter (TLC) and Dlco at 12 months than those treated on the general wards. There were, however, no significant differences in 6MWD and HRQoL between the two groups at 12 months. In addition, there were no differences in any functional parameters between ICU patients receiving and not receiving mechanical ventilation. Herridge et al reported that 20% of their ARDS survivors had minor abnormalities on CXRs at 1 year.

There are several limitations to this study. Firstly, we did not perform cardiopulmonary exercise testing (CPET), as many patients complained of generalized muscle weakness on initial follow-up. CPET would also be too labor-intensive for a large cohort of SARS survivors. Nevertheless, reduced pulmonary gas exchange has been detected with CPET in some survivors of SARS at 3 months with normal Dlco. Secondly, only 97 of 123 survivors (79%) in the cohort had completed the serial assessments over 12 months, and the results might not be representative of the entire cohort. Thirdly, we assessed respiratory muscle strength with mouth pressure, but low PEmax values do not always indicate expiratory muscle weakness and might result from technical difficulties such as mouth leakage. Lastly, we could not measure the effects of extrapulmonary factors (such as muscle deconditioning, steroid or viral-induced myopathy, cardiac diastolic dysfunction, critical illness polyneuropathy and/or myopathy) in the poor performance of the 6MWT. It is difficult to determine the contribution by psychological and motivational factors, as many patients are seeking compensation for occupation-related SARS.

In summary, this study has shown significant impairment of Dlco in 23.7% of SARS survivors, whereas their exercise capacity and health status were remarkably lower than the general population at 12 months after illness onset. The functional disability appears to be out of proportion to the degree of lung function impairment and may be due to additional factors such as muscle deconditioning, steroid-related musculoskeletal complications, critical illness-related neuropathy/myopathy, and other psychological factors. Further follow-up is needed to assess if these deficits are persistent.

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Canadian Health&Care Mall: Severe Acute Respiratory Syndrome on Pulmonary Function, Exercise Capacity, and Quality of Life in a Cohort of Survivors
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