The overall mortality from PF (J84) has been on the increase in Finland between the years 1998 and 2015 i.e. there were 136 PF deaths in the year 1998, but that number had more than doubled to 280 PF deaths in 2015 (183). In 1998, 69 (50.7 %) deaths occurred in males and 67 (49.3 %) in females as compared to the year 2015 when the majority i.e. 167 (59.6 %) of PF deaths occurred in males (183).
The official population of Finland at the end of the year 1998 was 5 159 646 and at the end of the year 2015, it was 5 487 308 people. From these numbers, one can calculate the overall mortality rates of PF as being 2.6 per 100 000 and 5.1 per 100 000 in the years 1998 and 2015, respectively (228).
Figure 6 presents the number of deaths from PF in Finland between the years 1998 and 2015.
Figure 6. The numbers of deaths from pulmonary fibrosis (ICD-10 code J84) in Finland between the years 1998 and 2015 according to data from Statistics Finland (183).
In the KUH area, the five-year overall mortality rate in 2003 – 2007 was 2.5 per 100 000 whereas between the years 2008 and 2012, it had almost doubled to 4.7 per 100 000.
When including only patients with IPF (ICD-10 code J84.1) as the underlying cause of death i.e. disease-specific mortality, the annual mortality rates were 1.7 per 100 000 in 2011 and 3.1 per 100 000 in 2012. The five-year mortality rates between the years 2003 – 2007 were 0.7 and 1.9 per 100 000 for females and males, respectively; between the years 2008 – 2012, the mortality rates were 1.85 per 100 000 for females and 3.3 per 100 000 for males.
The main underlying causes of death were IPF, CAD and lung cancer. The most common immediate causes of death were IPF, pneumonia and CAD. During the study period, a higher percentage of females (87.1 %) died from IPF as compared to males (54.7 %), i.e.
disease-specific mortality was higher in females. With respect to the 60 patients with CAD, 28.3 % had CAD as the underlying cause of death and 25.0 % as the immediate causes of death.
According to the medical records AEx was observed in 11 (12.7 %) and there was a suspicion of an AEx in 28 (35.4 %) patients with IPF as the underlying cause of death. AEx was observed in 7 (12.9 %) and a suspected AEx in 18 (33.3 %) patients with IPF as the immediate cause of death. More males than females had pneumonia as the immediate cause of death (Table 33).
0 50 100 150 200 250 300 350
Pulmonary fibrosis deaths in Finland 1998 - 2015
Total
Year
Table 33. Causes of death and acute exacerbations preceding death in males and females.
Causes of death obtained from death certificates and the information of acute exacerbations was gathered from medical records.
P-values calculated using Chi-squared test or Fisher test
a Between genders b sick sinus syndrome (N=1), cerebral infarction(N=1), aortic sclerosis (N=1), ileum strangulation (N=1), heart failure (N=1), drowning (N=1) c For any reason, including cor pulmonale d cerebral infarction (N=1), aortic rupture (N=1), ileum strangulation (N=1), hypotension (N=1), respiratory failure (N=1), drowning (N=1) e No HRCT confirmation
IPF, idiopathic pulmonary fibrosis; COPD, chronic obstructive pulmonary disease; HRCT, high-resolution computed tomography; AEx, acute exacerbation of IPF
Ex-smokers and current smokers had more often lung cancer as the underlying cause of death as compared to non-smokers. A trend towards a statistically significant difference was observed when comparing the underlying causes of death between non-smokers and current smokers (p=0.062 for IPF and p=0.091 for pneumonia). Non-smokers had more often IPF and less often pneumonia as the immediate cause of death as compared to ex-smokers.
No significant differences were observed in the causes of death between ex-smokers and current smokers (Table 35).
Table 35. Causes of death and acute exacerbations preceding death in patients with different smoking histories. Causes of death obtained from death certificates and the information of acute exacerbations was gathered from medical records.
Non-smokers
Pulmonary embolism 2 (4.7) 0.191
Colon cancer 2 (3.6) 0.342
Pulmonary embolism 2 (4.7) 0.191
Colon cancer 2 (3.6) 0.342
Other g 1 (2.3) 3 (5.5) 1 (6.7)
Exacerbations preceding death
AEx 5 (11.6) 6 (10.9) 0.370
Suspected AEx h 11 (25.6) 16 (29.1) 4 (26.7) 0.929
P-values calculated using Chi-squared test or Fisher test
a p-value between different smoking histories b p=0.045 between non-smokers and ex-smokers;
P=0.016 between non-smokers and current smokers c sick sinus syndrome (N=1), cerebral infarction(N=1), aortic sclerosis (N=1), ileum strangulation (N=1), heart failure (N=1), drowning (N=1) d p= 0.043 between non- and ex-smokers e p=0.007 between non- and ex-smokers, f For any reason, including cor pulmonale; g cerebral infarction (N=1), aortic rupture (N=1), ileum strangulation (N=1), hypotension (N=1), respiratory failure (N=1), drowning (N=1) h No HRCT confirmation
IPF, idiopathic pulmonary fibrosis; COPD, chronic obstructive pulmonary disease; HRCT, high-resolution computed tomography AEx, acute exacerbation of IPF
No differences were found in the causes of death between different GAP stages or between stages distinguished according to FVC % and DLco % at baseline.
More patients with a slow disease course had IPF as the underlying cause of death as compared to patients with a moderate disease course. More patients with a rapid disease course died from an AEx as compared to their counterparts with moderate and slow disease course (Table 36).
Table 36. Causes of death and acute exacerbations preceding death in patients with rapid (survival less than 2 years), moderate (survival 2 – 5 years) and slow (survival more than 5 years) disease course. Causes of death obtained from death certificates. The information of acute exacerbations was gathered from medical records.
Rapid (n=40) Moderate (n=42) Slow (n=45) p-value a
P-values calculated using Chi-squared test or Fisher test
a p-value between the groups of different disease progression subgroups b p=0.033 between slow and moderate disease progression subgroup c sick sinus syndrome (N=1), cerebral infarction(N=1), aortic sclerosis (N=1), ileum strangulation (N=1), heart failure (N=1), drowning (N=1) d For any reason, including cor pulmonale e cerebral infarction (N=1), aortic rupture (N=1), ileum strangulation (N=1), hypotension (N=1), respiratory failure (N=1), drowning (N=1) f p=0.013 between rapid and moderate disease progression subgroup g No HRCT confirmation h p=0.003 between rapid and moderate disease progression subgroup
IPF, idiopathic pulmonary fibrosis; COPD, chronic obstructive pulmonary disease; HRCT, high- resolution computed tomography; AEx, acute exacerbation of IPF
Fifty (43.5 %) patients died in a tertiary hospital, of which 4 (8.0 %) in ICU; 50 (43.5 %) patients died in a community hospital, 16 (13.9 %) at home and 1 (0.9 %) in a nursing home.
6 Discussion
IPF has been investigated actively during the 21st century. Since the first international guidelines for diagnosing and managing this disease were published in 2000, the diagnostic procedures and management of the patients have become more uniform all around the world. In addition, the guidelines have helped to characterize the disease more accurately (53). During these years, the diagnostic tools have been developing and CT imaging data has become more precise. The novel pharmacological treatments, pirfenidone and nintedanib, have increased the importance of early detection of the disease as well as prognostication of the course of disease. However, despite major efforts to develop accurate staging systems and prognostic models, it is still difficult to predict the course of the disease of an individual patient.
This study aimed to characterize a real-life cohort of patients with IPF in KUH hospital district. The clinical course of IPF patients was studied between the groups of difference in their observed lifetime in an attempt to identify clinical factors that would serve as predictors of mortality. In addition, the effect of comorbidities and smoking history were investigated to clarify their impact to the course of disease and causes of death. The utility of CPI and GAP staging was studied as well as in their comparison to the commonly used clinical variables in prognostication.