Lung (2014) 192:729–737 DOI 10.1007/s00408-014-9623-4

A Retrospective Study of Prognostic Factors in Patients with Interstitial Pneumonia Receiving Long-Term Oxygen Therapy Masayoshi Higashiguchi • Takashi Kijima • Hiromitsu Sumikawa • Osamu Honda • Toshiyuki Minami • Haruhiko Hirata • Koji Inoue • Izumi Nagatomo • Yoshito Takeda • Hiroshi Kida • Noriyuki Tomiyama Atsushi Kumanogoh



Received: 27 February 2014 / Accepted: 3 July 2014 / Published online: 24 July 2014 Ó Springer Science+Business Media New York 2014

Abstract Purpose We retrospectively analyzed patients with clinically diagnosed interstitial pneumonia to investigate the factors which contribute to the difference in prognosis from the initiation of long-term oxygen therapy (LTOT) among subtypes. Methods Seventy-six patients with clinically diagnosed idiopathic interstitial pneumonia (IIP; n = 49) or interstitial pneumonia associated with collagen vascular disease (CVD-IP; n = 27) in whom LTOT was initiated in our facility from January 1999 to December 2012 were analyzed. Results Patients with CVD-IP had significantly longer survival time from the initiation of LTOT than those with IIP with the median survival of 51.7 months versus 18.8 months, respectively. The 1-year survival rate was 92.4 % for patients with CVD-IP versus 76.5 % for those with IIP, and 2-year survival was 88.6 versus 36.0 %, respectively. The patterns classified with high-resolution computed tomography (HRCT) were not associated with prognosis. The association between pulmonary hypertension and prognosis was unclear. In results of the multivariate Cox analysis which included factors demonstrating p \ 0.1 in the univariate Cox analysis, male gender, low

M. Higashiguchi  T. Kijima (&)  T. Minami  H. Hirata  K. Inoue  I. Nagatomo  Y. Takeda  H. Kida  A. Kumanogoh Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan e-mail: [email protected] H. Sumikawa  O. Honda  N. Tomiyama Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan

body mass index, and the absence of collagen vascular disease (CVD) were significantly associated with poor prognosis. Conclusions After the initiation of LTOT, patients with IIP had poor prognosis regardless of the patterns classified with HRCT, while those with CVD-IP survived longer. Male gender, low body mass index, and the absence of CVD were the independent negative prognostic factors in patients with interstitial pneumonia receiving LTOT. Keywords Interstitial pneumonia  Collagen vascular disease  Long-term oxygen therapy  High-resolution computed tomography  Prognostic factors

Introduction Interstitial pneumonia (IP) is characterized by various patterns of the lung inflammation and fibrosis of known or unknown etiology, and it is classified accordingly into secondary IP or idiopathic IP (IIP). IP causes progressive respiratory failure, cor pulmonale, and death, and an optimal treatment has not yet been established. IIPs are further categorized into major IIPs, rare IIPs, and unclassified IIPs in the most recent American Thoracic Society/European Respiratory Society (ATS/ERS) statement [1]. The major IIPs are idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (NSIP), respiratory bronchitis-interstitial pneumonia, desquamative interstitial pneumonia, cryptogenic organizing pneumonia, and acute interstitial pneumonia. Among these types, IPF and idiopathic NSIP are the two most common. IPF, which is histologically characterized by a usual interstitial pneumonia (UIP) pattern, is associated with the worst prognosis [2, 3]. Collagen vascular disease (CVD) is an important

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cause of secondary IP, and it has been reported that an NSIP pattern is a more predominant histologic finding in IP associated with CVD (CVD-IP) compared to IIP [4, 5]. Long-term oxygen therapy (LTOT) is frequently initiated when patients with IP become hypoxemic due to disease progression. LTOT can ameliorate respiratory symptoms and may prolong survival [2, 6]. Most previous studies examining the survival of patients with IP have measured survival time from the date of diagnosis or surgical lung biopsy, where the baseline characteristics and clinical course of the patients may have been quite heterogeneous. In addition, although it has been shown that patients with NSIP or CVD-IP have a better prognosis compared to those with IPF [7–10], some of patients with NSIP or CVD-IP have poor response to the treatment and deteriorated to oxygen dependency. However, data are lacking about the prognosis of such refractory subtypes of NSIP or CVD-IP and it remains unknown whether such patients still have a better prognosis compared to those with IPF of similar severity. In this study, we have retrospectively evaluated survival rates after the initiation of LTOT among patients with IP and have clarified the prognostic factors in this clinical setting.

Methods Patients The records of Osaka University Hospital were searched for patients with clinically diagnosed IIP or CVD-IP in whom LTOT was initiated from January 1999 to December 2012. The diagnosis of IP was based on the findings of physical examination, laboratory tests, pulmonary function tests, and high-resolution computed tomography (HRCT) assessments. The diagnosis of CVD in CVD-IP patients was made according to established guidelines [11–15]. In our facility, patients who are anticipated to require oxygen therapy are routinely hospitalized and are evaluated with arterial blood gas, laboratory data, and HRCT. LTOT was initiated when the partial oxygen pressure in the arterial blood gas (PaO2) at rest under room air was \60 mmHg or when the percutaneous oxygen saturation (SpO2) was \90 % on exertion under room air accompanied by significant dyspnea. The date of LTOT initiation was defined as the date when patients were discharged with LTOT, and the survival time was measured from this date. Patients with IPs thought to be secondary to environmental exposure or drug toxicities and those with severe organ disease or active invasive cancer at the initiation of LTOT were excluded from the study. Clinical information of age, gender, duration from the diagnosis of IP to the initiation of LTOT, body mass index (BMI), spirometric results,

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smoking history, arterial blood gas data, Krebs von den Lungen-6 (KL-6), ultrasound cardiogram (UCG) data, right heart catheterization data, medications, and the causes of death was also obtained from the medical records. Akira’s criteria were used for the definition of acute exacerbation [16]. The institutional review board approved this study (ID number, 13332), which was also registered in UMIN as UMIN000012594. High-Resolution Computed Tomography Classification An expert thoracic radiologist at our facility (H.S.), who was not aware of the patients’ clinical data, evaluated the HRCT findings that were obtained during the introduction of LTOT. The HRCT images were classified as UIP pattern, possible UIP pattern, or pattern inconsistent with UIP based on the 2011 ATS/ERS statement [2]. Further, the presence of honeycombing was evaluated; honeycombing was defined as clustered cystic airspaces with well-defined walls in the subpleural regions. Statistical Analyses To compare groups, Welch’s test was used for continuous data and Fisher’s exact test was used for categorical data. Survival rates were estimated using the Kaplan–Meier method. The log-rank test was used to compare survival between groups. The prognostic factors were analyzed using univariate and multivariate Cox proportional hazards regression models. Factors with p values \0.1 in the univariate analysis were included in the multivariate analysis. All analyses were performed using the R statistical package, version 3.0.1 [17]. A p value \0.05 indicated statistical significance.

Results Patient Characteristics In total, 76 patients were identified as suitable for this study. The characteristics of the patients at the initiation of LTOT are shown in Table 1. Forty-nine patients had IIP and 27 had CVD-IP. The underlying CVDs were polymyositis/dermatomyositis (n = 9), systemic sclerosis (n = 9), rheumatoid arthritis (n = 5), primary Sjogren’s syndrome (n = 2), and mixed connective tissue disease (n = 2). The CVD-IP group included younger patients, a greater number of female patients, and fewer patients with an UIP pattern on HRCT versus the IIP group. Further, we observed a trend of more ex-smokers in the IIP group, but this was not statistically significant. The duration from the diagnosis of IP to the date of LTOT initiation was

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Table 1 Characteristics of the patients at the initiation of LTOT IIP (n = 49)

CVD-IP (n = 27)

p value

Median

72

63

\0.001*

IQR

69–77

55–74

Table 2 Prescribed medication for interstitial pneumonia at the initiation of LTOT IIP-UIP (n = 28)

IIPnon-UIP (n = 21)

CVDIP-UIP (n = 7)

CVD-IPnon-UIP (n = 20)

11

6

2

2

PSL

4

7

4

6

Pir

5

0

0

0

PSL ? AZA

0

0

1

2

Gender

PSL ? CP

1

1

0

1

Male

28

7

PSL ? CsA

3

4

0

8

Female

21

20

PSL ? MMF

0

0

0

1

PSL ? Pir

2

2

0

0

PSL ? AZA ? Pir

1

0

0

0

PSL ? CP ? Pir

0

1

0

0

PSL ? CsA ? Pir

1

0

0

0

Age (years)

No medication

Duration from the diagnosis to the initiation of LTOT (years) Median IQR

2.68 0.98–5.73

5.14

0.025*

1.30–10.13 0.015*

BMI Median

23.0

21.8

IQR

19.7–24.5

19.5–21.6

0.413

Smoking history Ex-smoker

31

10

Never-smoker

18

17

Median

56.0

54.6

IQR

47.5–66.4

47.4–65.1

Median

64.9

57.9

IQR

55.3–77.0

51.0–68.2

Median

27.4

28.0

IQR

20.6–32.9

12.0–51.5

Median

67.8

68.3

IQR

58.75–77.4

58.7–77.6

Median

40.9

39.2

IQR

37.7–45.8

35.2–43.0

Median

1,186

1,096

IQR

735–1,714

732–1,546

0.067

FVC % predicted 0.575

IIP idiopathic interstitial pneumonia, CVD-IP interstitial pneumonia associated with collagen vascular disease, non-UIP possible UIP pattern or pattern inconsistent UIP, PSL prednisone, Pir pirfenidone, AZA azathioprine, CP cyclophosphamide, CsA cyclosporin A, MMF mycophenolate mofetil

FEV1 % predicted 0.079

DLCO % predicted 0.515

PaO2 (mmHg) 0.807

PaCO2 (mmHg) 0.304

KL-6 (U/ml) 0.930

Honeycombing Yes

37

14

No

12

13

UIP

28

7

Possible UIP

3

1

Inconsistent with UIP

18

19

significantly longer in the CVD-IP group compared to in the IIP group. LTOT was not discontinued in any of the patients. The medications used for IP at the initiation of LTOT are listed in Table 2; steroid and immunosuppressant drugs (azathioprine, cyclophosphamide, cyclosporin A, and mycophenolate mofetil) were prescribed to significantly more patients in the CVD-IP group than in the IIP group (p = 0.011 for steroid and 0.044 for immunosuppressant). Pirfenidone was used only in the IIP group. Histologic examinations had been performed for six IIP patients, 4 at autopsy and 2 after surgical lung biopsy. All 6 of these patients had histologic UIP patterns. In this same group, the HRCT classification identified 4 patients with UIP patterns, one with a possible UIP pattern, and one with pattern inconsistent with UIP.

0.354

Survival

HRCT pattern 0.015*,a

LTOT long-term oxygen therapy, IIP idiopathic interstitial pneumonia, CVD-IP interstitial pneumonia associated with collagen vascular disease, IQR interquartile range, BMI body mass index, FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, DLCO carbon monoxide diffusing capacity, PaO2 partial oxygen pressure in the arterial blood gas, PaCO2 partial carbon dioxide pressure in the arterial blood gas, KL-6 Krebs von den Lungen-6, UIP usual interstitial pneumonia *Statistical significance a

UIP pattern versus possible UIP pattern or pattern inconsistent with UIP pattern

The survival times measured from the initiation of LTOT in the patients with IIP and those with CVD-IP are shown in Fig. 1. Patients with CVD-IP had significantly longer survival times compared to those with IIP (p \ 0.001; median survival, 51.7 months in CVD-IP versus 18.8 months in IIP). The 1-year survival rate was 92.4 % for CVD-IP patients versus 76.5 % for IIP patients, and the 2-year survival rate was 88.6 versus 36.0 %, respectively. The association between the HRCT findings and prognosis was examined. The survival curves according to the HRCT patterns in the IIP group and in the CVD-IP group are shown in Fig. 2a, b, respectively. The HRCT pattern

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presence of honeycombing was not significantly associated with prognosis in either the IIP group (p = 0.551) or the CVD-IP group (p = 0.940) (Fig. 3). The causes of death are shown in Table 3. The most frequent cause of death in the IIP group was acute exacerbation, followed by gradual progression of the disease; these causes of death were rarely observed in the CVD-IP group. Pulmonary Hypertension

Fig. 1 Survival curves for patients with IIP (n = 49) and those with CVD-IP (n = 27). Patients with CVD-IP had significantly longer survival times than those with IIP (p \ 0.001). Median survival time was 51.7 months in CVD-IP group versus 18.8 months in IIP group. MST median survival time, mo months

UCG data at the initiation of LTOT were available in 47 patients (28 patients with IIP and 19 patients with CVDIP); 3 of these patients were also evaluated with right heart catheterization. Pulmonary hypertension (PH) was defined as follows: definite PH; mean pulmonary arterial pressure equal to or greater than 25 mmHg and suspected PH; tricuspid regurgitation pressure gradient [30 mmHg (18). There were 14 patients (11 IIP and 3 CVD-IP) with suspected PH and 2 patients (1 IIP and 1 CVD-IP) with definite PH. The presence of PH was not significantly associated with survival in either IIP (p = 0.327) or CVDIP (p = 0.866) (Fig. 4a, b). Prognostic Factors

based on the 2011 ATS/ERS statement was not significantly associated with prognosis in either the IIP group (p = 0.633) or the CVD-IP group (p = 0.333). Further, the

On univariate Cox analysis, older age, male gender, UIP pattern on HRCT, the absence of CVD, and higher partial

Fig. 2 a Survival curves for patients with IIP by HRCT classification: UIP pattern (n = 28) versus possible UIP pattern or pattern inconsistent with UIP (n = 21). Survival time did not differ significantly between the groups (p = 0.633). Median survival time was 16.4 months in patients with UIP pattern versus 19.7 months in patients with possible UIP pattern or pattern inconsistent with UIP.

b Survival curves for patients with CVD-IP by HRCT classification: UIP pattern (n = 7) versus possible UIP pattern or pattern inconsistent with UIP (n = 20). Survival time did not differ significantly between the groups (p = 0.333). Median survival time was 46.0 months in patients with UIP pattern versus 76.6 months in patients with possible UIP pattern or pattern inconsistent with UIP

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carbon dioxide pressure in the arterial blood gas were significantly associated with a poor prognosis (Table 4). When all factors with p \ 0.1 on univariate analysis were analyzed by multivariate Cox analysis, male gender, low BMI, and the absence of CVD remained significantly associated with a poor prognosis (Table 5).

Discussion This retrospective study focused on prognostic indicators after the initiation of LTOT in patients with IP. In previous studies, IPF had the worst prognosis when survival from diagnosis or surgical lung biopsy was examined, with a median survival of 2–4 years [8–10, 19]. A better prognosis has been reported for CVD-IP [7, 8] or IIPs other than IPF [9, 10]. However, there was probably a great deal of heterogeneity in the clinical course and baseline characteristics of the patients because these survival times might have been affected by delayed referral to specialized centers or the timing of lung biopsy. In the sense that LTOT is likely initiated at similar disease severity among patients, survival times recorded from the time of initiation of LTOT, as were analyzed in the present study, are clinically important. The better prognosis of CVD-IP compared to that of IIP was previously thought to be associated with the histologic

Fig. 3 a Survival curves for patients with IIP by the presence of honeycombing. Survival time did not differ significantly between the groups (p = 0.551). Median survival time was 16.4 months in patients with honeycombing (n = 37) versus 19.7 months in patients without honeycombing (n = 12). b Survival curves for patients with

733 Table 3 Causes of death IIP Acute exacerbation

CVD-IP

15

2

Gradual progression of disease

7

0

Lung infection

2

6

Lung cancer

1

0

Sudden death

4

3

Uncertain

6

1

IIP idiopathic interstitial pneumonia, CVD-IP interstitial pneumonia associated with collagen vascular disease

predominance of the NSIP pattern in CVD-IP; however, better survival has been observed even in patients who had CVD-IP with histologic UIP patterns (CVD-UIP). Song et al., who retrospectively analyzed 39 cases of CVD-UIP and 61 cases of IPF with a histologic UIP pattern (IPF-UIP) diagnosed by surgical lung biopsy, found that CVD-UIP had a better prognosis compared to IPF-UIP [8]; the median survival time was 143.8 months for CVD-UIP versus 40.1 months for IPF-UIP (p = 0.001). In a study, by Park et al. [7] that included 93 cases of CVD-IP and 269 cases of IIP diagnosed by surgical lung biopsy, the mean survival times were 125.5 months for CVD-UIP and 66.9 months for IPF-UIP (p = 0.001). On the other hand, IIP and CVD-IP with histologic NSIP patterns have been found to have comparable survival rates [7], with 3-year

CVD-IP by the presence of honeycombing. Survival time did not differ significantly between the groups (p = 0.940). Median survival time was 51.7 months in patients with honeycombing (n = 14) versus 76.6 months in patients without honeycombing (n = 13)

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Fig. 4 a Survival curves for IIP patients with pulmonary hypertension (PH) (n = 12) and those without PH (n = 16). Survival time did not differ significantly between the groups (p = 0.327). b Survival

curves for patients with CVD-IP patient with PH (n = 4) and those without PH (n = 15). Survival time did not differ significantly between the groups (p = 0.866)

Table 4 Results of univariate Cox analysis

Table 5 Results of multivariate Cox analysis

HR

95 % CI

p value

Age per 5 years

1.28

1.11–1.47

0.001*

Age per 5 years

1.13

0.96–1.33

0.119

Female gender

0.50

0.28–0.89

0.017*

Female gender

0.48

0.24–0.95

0.036*

BMI per 5

0.67

0.44–1.05

0.082

BMI per 5

0.43

0.24–0.76

0.003*

UIP

1.87

1.05–3.33

0.033*

UIP

0.93

0.43–2.03

0.874

Presence of honeycombing

1.76

0.89–3.46

0.101

Presence of CVD

0.17

0.07–0.43

\0.001*

Presence of CVD

0.20

0.10–0.41

\0.001*

PaCO2 per 5 mmHg

1.20

0.88–1.64

0.236

FVC per 5 % predicted FEV1 per 5 % predicted

1.02 1.04

0.93–1.12 0.95–1.14

0.635 0.336

DLCO per 5 % predicted

0.99

0.89–1.12

0.982

HR hazard ratio, CI confidence interval, BMI body mass index, UIP usual interstitial pneumonia, CVD collagen vascular disease, PaCO2 partial carbon dioxide pressure in the arterial blood gas

PaO2 per 5 mmHg

0.98

0.87–1.09

0.740

* Statistical significance

PaCO2 per 5 mmHg

1.44

1.10–1.88

0.007*

KL-6 per 100 U/ml

0.99

0.96–1.02

0.516

HR hazard ratio, CI confidence interval, BMI body mass index, UIP usual interstitial pneumonia, CVD collagen vascular disease, FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, DLCO carbon monoxide diffusing capacity, PaO2 partial oxygen pressure in the arterial blood gas, PaCO2 partial carbon dioxide pressure in the arterial blood gas, KL-6 Krebs von den Lungen-6 * Statistical significance

survival rates of 77.6 and 88.9 %, respectively, and 5-year survival rates of 67.4 and 81.5 %, respectively (p = 0.2). These results suggest that CVD-UIP has a better survival than IPF (IPF-UIP), which is consistent with the results of Song et al. [8]. Taken together, these results indicate that the presence of CVD is associated with a better prognosis in patients with UIP histology, but not in those with NSIP

123

HR

95 % CI

p value

histology. However, the survival times measured in most studies might have been unreliable because the timing of the IP diagnosis is usually obscure. For instance, CVD-IP is often diagnosed while the underlying CVD is being followed; therefore, the survival time could be accordingly overestimated. Our study suggested that CVD-IP is still associated with a better prognosis than IIP even after these diseases have worsened to an oxygen-dependent state. Although surgical lung biopsy is regarded as the most reliable method for classifying disease phenotypes, we often prefer to use HRCT findings for making classification decisions because of the risks associated with the surgical procedure, especially in patients with severe disease. The association between HRCT findings and prognosis is clinically important, and HRCT classifications have been

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evaluated against histologic findings in several studies. In a report by Flaherty et al. [20], the HRCT images in 73 patients who had IIP with histologically proven UIP patterns (IIP-UIP) were classified as definite UIP, probable UIP, intermediate, probable NSIP, and definite NSIP patterns. The patients with HRCT patterns interpreted as definite UIP or probable UIP had significantly shorter survival times compared to those with other HRCT patterns. Therefore, this study suggests that HRCT patterns can be associated with prognosis even in patients with UIP on histology. However, Sumikawa et al. [21] reported conflicting results. These authors categorized the HRCT images of patients with histologically proven IPF as definite UIP, consistent with UIP, and suggestive of an alternative diagnosis, but they did not find any significant difference in survival among the 3 HRCT patterns. We failed to find differences in survival between the HRCT patterns based on the 2011 ATS/ERS statement and between the presence and absence of honeycombing in our cohort. Although histological examinations were performed for few patients in our study, we propose 2 possible explanations for the results regarding the HRCT patterns. First, many of the patients with a HRCT pattern inconsistent with UIP might have had histologic UIP. Second, the prognosis might have been poor even for patients with histology other than UIP once they became oxygendependent. In our study, acute exacerbation was the most frequent cause of death for patients with IIP, while it was rare in those with CVD-IP. Acute exacerbation is a devastating event and is an important cause of death, especially in IPF. Daniels et al., who reviewed autopsy reports from 42 patients with IPF, reported that respiratory-related causes accounted for 64 % of deaths; among these respiratory-related causes, acute exacerbation occurred with the highest frequency, followed by pneumonia and gradual progression of disease [22]. Although acute exacerbation is known to occur in patients with CVD-IP, it occurs at a lower frequency in CVD-IP patients compared to in patients with IPF [23]; this may partly account for the better prognosis of CVD-IP observed in our cohort. In our study, male gender, low BMI, and the absence of CVD were independently associated with a poor prognosis after adjusting for confounders. We excluded the factor of the presence of honeycombing from the multivariate analysis although the p value of the factor in the univariate analysis was almost near 0.1. Otherwise, including both factors of UIP pattern and the presence of honeycombing can cause a problem of multicollinearity because there was a strong correlation between these two factors (p \ 0.001 on Fisher’s exact test). Even when the presence of honeycombing was included in the multivariate analysis, the

735

results did not change significantly (data not shown). Previous studies have also reported that gender and BMI are significant prognostic factors [24, 25]. Conversely, Kondoh et al. [26] who retrospectively analyzed 110 patients with IPF, showed that high BMI was an independent risk factor for acute exacerbation of IPF (hazard ratio, 1.20; 95 % confidence interval, 1.46–5.85; p \ 0.001), but it was not associated with survival (hazard ratio, 0.97; 95 % confidence interval, 0.88–1.07; p = 0.590) [26]. Pulmonary function data, particularly carbon monoxide diffusing capacity (DLCO) \40 % of predicted value, are also reported to be useful prognostic indicators [2, 18]. However, no correlation between spirometric data and prognosis was found in our study, possibly due to patient selection. Our study included patients receiving LTOT, and more than 85 % of these patients had severely impaired pulmonary function, with DLCO \40 % of predicted value. Thus, the usefulness of a pulmonary function test as an independent predictor of survival was likely negated in this population. PH is a common condition and has been demonstrated to be an important poor prognostic factor in IPF [27] and systemic sclerosis [28]. However, the association between PH and survival was unclear in this study. This may be because few patients underwent evaluation for pulmonary hemodynamics, and most patients were evaluated with UCG. UCG is often performed to evaluate pulmonary hemodynamics as a substitutive method for right heart catheterization because it is less invasive and less time consuming. However, UCG is a less reliable measure than catheterization for detecting PH [19]. This study had several limitations. First, this was a single-center retrospective study consisting of a small sample size. Second, histologic examinations were not performed in the majority of the patients. Finally, the association between treatments other than LTOT and the prognosis was not examined because evaluating treatment effects in a study with a retrospective design would be difficult and would yield potentially misleading results. However, even with these limitations, our study provides clinically useful information regarding the prognosis from the initiation of LTOT and the prognostic factors in this clinical setting because the data reflect real clinical practice.

Conclusions The present study showed that the prognosis of oxygendependent IP is poor, especially in patients with IIP, regardless of the HRCT pattern. Male gender, low BMI, and the absence of CVD were the independent negative prognostic factors in patients with IP receiving LTOT. It is

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important that we continue to advance our understanding of the pathogenesis of IPs and develop novel treatments.

Conflict of interest

None.

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A retrospective study of prognostic factors in patients with interstitial pneumonia receiving long-term oxygen therapy.

We retrospectively analyzed patients with clinically diagnosed interstitial pneumonia to investigate the factors which contribute to the difference in...
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