Table 13 presents the radiological diagnoses in conjunction with histological diagnoses of the 132 patients included in this study.
Table 13. Ultimate diagnoses based on clinical, radiological and histological findings, N (%) of patients.
HRCT, high-resolution computed tomography; UIP, usual interstitial pneumonia; IPF, idiopathic pulmonary fibrosis
The diagnosis of IPF was confirmed by the presence of a definite UIP pattern in HRCT in 81 (61.4 %) patients and in 4 (3.0 %) patients, the possible UIP pattern in HRCT was confirmed UIP in the histological analysis. In twelve (9.1 %) patients who had been assessed as not UIP in HRCT, histology indicated that they had definite UIP; in one patient (0.8 %) histology was indicative of UIP, but the HRCT images could not be confidently interpreted due to their low quality. Twenty-five (18.9 %) patients with possible UIP in HRCT, but without histological samples, as well as 9 (6.8 %) patients with not UIP according to HRCT were re-evaluated in the MDD in order to confirm the IPF diagnosis (Table 14). The HRCTs of the patients with the radiological pattern of not UIP have been recently re-analyzed by another experienced radiologist. Seven of the nine cases with not UIP in the first evaluation were re-evaluated to be possible or definite UIP. The kappa coefficient for the agreement between the two radiologists was moderate (κ= 0.555).
46 Table 14. The reasoning for including patients with not usual interstitial pneumonia (UIP) patterns in high-resolution computed tomography (HRCT) into the study. Decision was based on radiological diagnosis, treatment, course of disease and causes of death. Gender (age), smoking Atypical features in HRCTTreatment and survival Causes of deathMDD decision 1. Female (76), non-smoker First HRCT:Somegroundglass, peripheral and peribronchovascular fibrosis, some mosaic perfusion. Follow-up HRCT: upper- and mid-lung predominance, honeycombingabsent onlyfrom left upperlung section.
Corticosteroids without response, cyclophosphamide included but terminated after 3 months due to side effects. Survival 100 months.
J84.1 IPF Inconsistent distribution, but typical UIP features follow-upHRCT. responseto treatmen exposures excluded. 2. Male (70), ex-smoker Basalreticulationandemphysema,somebasal honeycombing in the right lung. Corticosteroids,without response, survival 64 months.
J84.1 IPF and confounding CAD and HF
Extentofemphysem interferingwi interpretation, distributi of honeycombing uneven, otherwise typical UIP. 3. Male (59), current smoker The distribution of honeycombing was upper- and mid- lung predominant. No treatment.Survival 55 months. I21 Acute coronary syndrome, confounding J84.1 IPF Thedistribution honeycombingwa atypical, otherwise UIP. 4. Female (82), non-smoker Some groundglassandmosaic attenuation,heart failure was the reason forthesuboptimal image quality.
No treatment. Extensive fibrosis that lead to death in 4 months.
J84.1 IPF, confounding HFHeart failure interfer with the interpretation of HRCT. 5. Female (84), non-smoker No honeycombing, basal reticulation. Some ground glass. No treatment, survival 54 months. J84.1 IPF, confounding HFHoneycombingabse some ground glass (hear failure) otherwise typical 6. Female (78), non-smoker Ground glass, basal reticulation, some honeycombing. Corticosteroids without response. Survival 26 months.
J84.1 Respiratory failure due to IPFHeart failure (grou glass) interferedwi interpretation. 7. Male (73), ex-smoker Suboptimal image quality. Distribution of honeycombing upper- and mid-lung predominant. Corticosteroids andNAC without response. Survival 9 months.
I25 CAD, confounding J84.1 IPF Atypicaldistribution honeycombing. 8. Male (75), ex-smoker Atypicaldistributionofhoneycombing, extensive emphysema in some sections.Pirfenidone. Survival 38 months. I25 CAD, confounding J84.1 IPF Atypicaldistribution honeycombing. 9. Female (67), non-smoker First HRCT: Suboptimal image quality, distribution of reticulation and honeycombing atypical. Follow-up HRCT: similar findings, extensive fibrosis.
No treatment.Survival 60 months. J18.9 Pneumonia and J84.1 IPF Atypicaldistribution honeycombing. HRCT, high-resolution computed tomography; IPF, idiopathic pulmonary fibrosis; MDD, CAD, coronary artery disease; HF, heart failure; UIP, usual interstitial pneumonia
5.1.2 Prevalence and incidence
In Northern Savo district which is home to 248 000 people, the prevalence of IPF was 13.7 per 100 000 on 31.12.2012 when 34 patients were alive with an IPF diagnosis. In the year 2011, the incidence was 4.8 per 100 000 whereas in the year 2012, it was 2.0 per 100 000. The annual number of new IPF diagnoses varied between 5 and 13 in KUH with the mean incidence being 4.0 per 100 000 between the years 2002 and 2012.
5.1.3 Demographics
The demographics of the study population are presented in table 15. Smoking history was unknown in 4 (3.0 %) patients. Baseline spirometry results were available from 126 patients and the results of diffusion capacity test were available from 124 patients. PFT values were missing due to frailty of the patients. In addition, one patient died suddenly before performing the PFT. The majority of patients were males and ex-smokers. Median survival was 42 months. Findings from the BAL samples of 55 patients are presented in Table 16.
Table 15. Demographics of the study population at baseline (N=132).
Mean age (SD) 70.5 (9.8)
Males N(%) 97 (73.5)
Median survival (mo)(range) 42.0 (32.6 – 51.5) Smoking history N (%) Non-smoker 44 (33.3)
Lung transplantations N (%) 3 (2.3) Respiratory hospitalizations N (%) 88 (66.6) Mean N of hospitalizations (%) 1.3 (1.6) Mean time to first hospitalization (mo)(SD) 29.0 (34.2)
N, number; mo, months; FVC, forced vital capacity; l, liters; SD, standard deviation; pred, predicted; ml, milliliters; min, minute; kPa, kilo Pascal; FEV1, forced expiratory volume in one second; DLco, diffusion capacity of carbon monoxide; CPI, composite physiologic index; HRCT, high-resolution computed tomography; BAL, bronchoalveolar lavage; TBB, transbronchial biopsy; VATS, video-assisted thoracoscopic surgery
Table 16. Cell counts of the BAL samples (N=55).
A total of 115 (87.1 %) deaths occurred during this study and three patients, one of whom is deceased, received a lung transplant; their characteristics are presented in table 17.
Table 17. Characteristics of the patients receiving a lung transplant.
Patient 1 Patient 2 Patient 3
Operation type Heart-lung Double lung Double lung
Gender Male Male Male
Age at diagnosis 50 38 59
Smoking history Current smoker Current smoker Ex-smoker FVC at baseline (l/%) 3.15 / 61 4.39 / 74 3.34 / 68
Treatment before LTX Corticosteroid and cyclophosphamide –>
a absolute value missing from patients’ files.
FVC, forced vital capacity; l, liter; %, percent predicted; FEV1, forced expiratory volume in one second; DLco, diffusion capacity of carbon monoxide; HRCT, high-resolution computed tomography; UIP, usual interstitial pneumonia; BAL, bronchoalveolar lavage; SLB, surgical lung biopsy; VATS, video-assisted thoracoscopic surgery; LTX, lung transplantation; AZA, azathioprine; NAC, N-acetylcysteine
5.1.4 Management of the patients
A substantial minority, 42 (31.8 %), of the patients did not receive any pharmacological treatment for IPF. Most of the patients received the pharmacological therapies commonly used for IPF between 2000 and 2011 i.e. corticosteroid, azathioprine, NAC and cyclophosphamide. A total of six patients received pirfenidone and three patients received nintedanib. Two patients from the six that were treated with pirfenidone received also nintedanib, i.e. four patients were treated only with pirfenidone and one patient with nintedanib. A total of 125 patients (94.6 %) did not receive the currently recommended pharmacological treatment for IPF due to the fact that they were diagnosed and treated before these medications became available. The pharmacological treatments and oxygen therapy prescribed for the patients are presented in table 18.
Table 18. Pharmacological treatment for IPF (N=132).
Medication N / %
Combined with prednisone as only medication
Azathioprine 14 / 10.6
Cyclophosphamide + Corticosteroids 2 / 1.5 After triple therapy
a Azathioprine, N-acetylcysteine and corticosteroids, b fentanyl, oxycodone
There were no statistically significant survival differences between patients who received corticosteroids, cyclophosphamide, triple therapy or NAC alone as compared to patients who did not receive these therapies.