The survival time of patients with IPF varies depending on diagnosis time. That is, it depends on the time of radiological abnormality, symptom onset, and diagnosis. It was reported that reticular opacity of the bilateral base shown in chest X-ray occurred several years before the onset of symptoms, and the symptoms began 1,000 days after radiologic abnormalities in patients who were diagnosed with IPF via biopsy or chest X-ray
4. In addition, many studies reported that the symptoms occurred 1~2 years before being diagnosed with IPF
5-12. Thus, IPF was reported to be diagnosed five or more years after the onset of symptoms
4. A comparison of the survival following its diagnosis showed that the median value of the survival time after symptom onset was approximately 48 months or less. Studies that were conducted following the classification of new idiopathic interstitial pneumonia reported that the median value of the survival time was 2~4 years, and that the 5-year survival rate was 20~40%
6-12. In addition, patients with IPF had high mortality, but the change in pulmonary function was insignificant
13,14. This is likely to be attributable to the fact that IPF showed stepwise progression rather than gradual progression, thereby resulting in high mortality
15. Therefore, an intensive management of IPF is important during the aforementioned acute stage.
The acute exacerbation of IPF means the sudden deterioration of underlying pulmonary diseases, which can secondarily occurs following the occurrence of infection, pulmonary embolism, pneumothorax, and heart failure
16. According to 2008 report on patients with idiopathic interstitial pneumonia, the death of patients with IPF were reported to be caused by respiratory failure 44%, pneumonia 31%, lung cancer 9%, cardiovascular disease 5%, and others 10% due to exacerbation. It was, however, difficult to distinguish acute exacerbation with pulmonary infection
2. Meanwhile, acute exacerbation occurs without clear reason
17-19, and this acute exacerbation stage occurs from time to time, and is also correlated with high mortality
17-24. A follow-up study conducted on 168 patients with IPF reported that 21% of the patients died during a period of 76 weeks (median), of whom 47% died of acute exacerbation
25. According to the results of studies on the prognosis of IPF, various factors, such as old age, male, dyspnea, smoking history, reduced pulmonary function, radiological abnormality, increased neutrophils or eosinophils in the bronchoalveolar lavage, honeycombing opacity on HRCT, and fibroblast foci on biopsy, were shown to be associated with poor prognosis
26-28. In this study, however, as bronchoalveolar lavage and/or surgical biopsy were rarely conducted, it was impossible to investigate the correlation with these factors. Among the factors that have been known to be associated with prognosis, the age, gender, pulmonary function, and presence of symptoms showed no statistical significance. Meanwhile, the patients with underweight had poorer prognosis. However, few studies have been conducted to investigate the correlation of BMI with prognosis in patients with IPF. BMI, which is calculated by dividing body weight (kg) by height (m)
2, is used as a marker that is measured by the World Health Organization for obesity management. As it can easily identify the nutritional state of patients, it is also used for checking malnutrition in addition to obesity. Patients are classified into underweight (<18.5 kg/m
2), normal (18.5~24.99 kg/m
2), overweight (25~29.99 kg/m
2), and obese status (≥30 kg/m
2)
29. As the correlation of chronic obstructive pulmonary disease (COPD) with BMI has been well known, BODE index that is comprised of BMI, airway obstruction, dyspnea, and exercise capacity has played an important role as a predictor of all-cause mortality in patients with COPD. Patients with moderate or severe COPD commonly have underweight. This was reported to be associated with increased metabolism and energy consumption as a result of systemic inflammatory response associated with pulmonary diseases. In addition, decreased pulmonary function was reported to be associated with decreased survival time in cystic fibrosis patients with malnutrition status
30-32. However, few studies have been conducted to investigate the correlation of BMI with survival time in patients with IPF. Cano et al.
33 reported that BMI was associated with prognosis of patients with restrictive pulmonary impairment, and that the BMI was one of mortality predictors in 446 patients who had chronic respiratory failure due to various causes. Among the aforementioned patients, 162 patients had restrictive pulmonary impairment
33, but most of whom were patients with chest wall disorders or kyphoscoliosis. Unfortunately, in that study, as the ratio of patients with interstitial lung disease or IPF was not shown, and the result was obtained from patients who had chronic respiratory failure due to various causes, it was difficult to directly correlate BMI with mortality risk caused by IPF
33. It was reported that high BMI contributed to the extension of the survival time of patients with IPF
34, and that malnutrition status caused thymic atrophy and reduced T-lymphocyte function, thereby increasing infection risk and decreasing the survival
35,36. Although it is difficult to make a conclusion on the association of BMI with the prognosis of IPF based on the results of the aforementioned studies alone, a further study is required to investigate the association of BMI with the prognosis of IPF. The guidelines of the ATS and ERS (2011) classified risk factors of mortality into two groups; baseline factors include level of dyspnea, DLco<40% predicted, desaturation≤88% during 6-minute walk test, extent of honeycombing on HRCT, and pulmonary hypertension, and longitudinal factors include increase in level of dyspnea, decrease in FVC by >10% absolute value, decrease in DLco by >15% absolute value, and worsening of fibrosis on HRCT. However, no assessment criteria for follow-up interval of HRCT or extent of fibrosis on HRCT has been established yet
2. It is necessary to diagnose disease progression by assessing the status of patients in an interval of 4~6 months. In the case of clinical exacerbation, it is necessary to check dyspnea, O
2 saturation, FVC, and DLco in a shorter interval. If 6-minute walk test is available, it is also recommended
2. As echocardiography, which is conducted in patients with interstitial lung disease to assess pulmonary arterial hypertension, is not accurate
37, echocardiography alone is not recommended for assessing pulmonary arterial hypertension. Disease such as lung cancer, coronary artery disease, or pulmonary embolism may affect prognosis, but it is unclear if annual HRCT test to check concurrent disease is useful
2. It was reported that IPF patients with concurrent emphysema had poorer prognosis than those without emphysema. A long-term oxygen therapy could be required to treat both diseases, and the both diseases could have pulmonary hypertension as a concurrent disease. As emphysema, however, did not significantly affect patient survival, it is unclear if emphysema is a factor representing poor prognosis
2,38,39. In this study, five and two patients with emphysema were included in the survival and death groups, respectively, which showed that the number of patients with emphysema was higher in the survival group than in the death group. However, due to the small patient number, it was statistically insignificant. Although all patients in this study were evaluated for survival status, the number of subject was so small that selection bias could have occurred. In addition, the multivariate analysis showed that among factors that were considered correlated with prognosis in previous studies, the presence of respiratory symptom and decreased pulmonary function at the time of diagnosis were not associated with prognosis, but low BMI and radiological exacerbation were associated with prognosis. Although this result seems to be inconsistent with the previous results, it is meaningful as it shows a possibility that BMI could be associated with not only COPD but also IPF. Furthermore, it could be helpful for determining the interval to conduct HRCT.
In conclusion, patients who had low BMI at the time of diagnosis and patients who showed radiologic progression on follow-up CT before 36 months after diagnosis had poor prognosis. Thus, these patients should be more carefully managed to reduce the risk of acute exacerbation.