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ORIGINAL ARTICLE

Correlation of high resolution CT patterns with

pulmonary function tests in patients with interstitial

lung diseases

Khaled Hussein

a

, Lamiaa H. Shaaban

a,*

, Ehab Mohamed

b

a

Chest Department, Assiut University Hospital, Assiut, Egypt

b

Diagnostic Radiology Department, Assiut University Hospital, Assiut, Egypt

Received 23 December 2015; accepted 28 January 2016 Available online 23 April 2016

KEYWORDS

High resolution CT (HRCT); Interstitial lung diseases (ILDs);

Pulmonary function

Abstract Background: Interstitial lung diseases (ILDs) refer to a broad category of lung diseases characterized by exertional dyspnea, different interstitial patterns on high resolution computed tomography (HRCT), and abnormal pulmonary functions.

The aim of this study: This is to correlate the radiological pattern and extent of involvement of ILDs with pulmonary function tests and verify the radiological functional relationship.

Patients and methods: This is a prospective descriptive study which was conducted upon 44 patients agedP18 years, who were diagnosed to have interstitial lung diseases (ILDs), all of them were admitted to Chest Department, Assiut University Hospitals between June 2014 and May 2015. They were classified into three groups according to the predominant pattern on HRCT: Group I: Fibrotic pattern including reticular pattern and/or honeycombing, Group II: Ground glass pattern, Group III: Nodular pattern. Pulmonary function tests including; forced spirometry, total lung capacity (TLC), residual volume (RV) and diffusing capacity for carbon monoxide (DlCO) also O2saturation via pulse oximetry were done for all patients.

Results: In this study 44 patients with ILDs were included, their mean age was 45.7 years, most of them were male (63.6%) and non smoker (59.1%) with mean SpO287.8%. the most frequent

HRCT pattern was the fibrotic one including reticular and honey combing (45.5%) followed by ground glass pattern (36%) and the least frequent one was the nodular pattern (18.2%). There was significant positive correlation between TLC and DLCO in fibrotic pattern (P value = 0.000), while no correlation could be detected between them in the other two patterns. Moreover, there was a significant positive correlation between DLCO and SpO2 in all different patterns

(P value = 0.000).

Conclusion: HRCT patterns and degree of lung involvement of ILDs correlate with pulmonary func-tion parameters. Lung volumes are lower in fibrotic lesion regardless the degree of lung involvement,

* Corresponding author.

Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis. H O S T E D BY

The Egyptian Society of Chest Diseases and Tuberculosis

Egyptian Journal of Chest Diseases and Tuberculosis

www.elsevier.com/locate/ejcdt www.sciencedirect.com

http://dx.doi.org/10.1016/j.ejcdt.2016.01.014

0422-7638Ó 2016 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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while DLCO among different patterns were dependent upon the degree of lung involvement. Restrictive pulmonary dysfunction correlate with gas exchange in fibrotic pattern while in ground glass one, gas exchange is independent on lung volumes.

Ó 2016 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Interstitial lung diseases (ILDs) refer to a broad category of lung diseases rather than a specific disease entity. These disor-ders are characterized by exertional dyspnea, interstitial pat-terns on high resolution computed tomography (HRCT), and abnormal pulmonary functions with restrictive ventilatory defect and decreased diffusing capacity for carbon monoxide (DLCO)[1,2].

Recent classification of ILDs recommended the utilization of four categories: (1) ILDs of a known cause (such as drugs, associated with a collagen vascular disease, environmental exposure, etc.); (2) granulomatous ILDs (such as sarcoidosis); (3) rare ILDs with well-defined clinicopathologic features (such as pulmonary histiocytosis-x, lymphangioleiomyomato-sis); and (4) the idiopathic interstitial pneumonias (IIPs) [3]. IIPsare further subdivided into seven subtypes. Of these, the most common patterns are usual interstitial pneumonia (UIP) called idiopathic pulmonary fibrosis (IPF) and nonspeci-fic interstitial pneumonia (NSIP)[4].

The most common HRCT patterns seen in ILDs are the lin-ear/reticular opacities, cystic lesions, ground-glass opacities and nodular pattern.

Pulmonary function testing is often used and recom-mended in the management of patients with ILDs [5]. The pattern of lung function impairments does not allow a speci-fic diagnosis to be made, but rather enables one to assess the severity of lung involvement. The pattern and quantitative relationships of the impairments of lung volumes and DLCO also allow defining coexisting complication like pulmonary hypertension [6].

A Few studies were conducted to correlate HRCT pattern with pulmonary functions. Hansell et al. tried to correlate the pattern and extent of abnormalities on HRCT with pul-monary function tests in subacute and chronic hypersensitivity pneumonitis and concluded that areas of decreased attenua-tion and mosaic pattern are an important CT finding that cor-related to obstructive functional abnormalities[7]. Also, more recent studies were conducted to correlate HRCT pattern and pulmonary function tests in scleroderma[8], and rheumatoid arthritis[9].

The aim of this study is to correlate the radiological pattern and extent of involvement of ILDs with pulmonary function tests and verify the radiological functional relationship. Patients and methods

This is a prospective descriptive study which was conducted upon 44 patients aged P18 years, who were diagnosed to have interstitial lung diseases (ILDs) with their high

resolution computed tomography (HRCT) of the chest had one or more of the following patterns: Fibrotic pattern (reticular and/or honeycombing), ground glass pattern, and nodular pattern. All of them were admitted to Chest Department, Assiut University Hospitals between June 2014 and May2015.

Exclusion criteria were pregnancy; acute exacerbation of IPF; consolidation; predominant cystic pattern as lymphangi-oleiomyomatosis and pulmonary langerhans histiocytosis; pri-mary pulmonary hypertension; diabetes mellitus; and cardiac disease.

They were classified into three groups according to predom-inant pattern on HRCT:

GroupI: Fibrotic pattern including reticular pattern and/ or honeycombing.

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All enrolled patients were subjected to:

(1) Thorough history taking and physical examination. (2) Chest HRCT: sections of 1.5 mm were acquired at

10-mm intervals in the supine position. Scans were eval-uated independently by two observers. According to the extent of involvement on HRCT, a modified quantita-tive scale was used[10]. The findings were assigned as 0; normal, 1; Minimal disease (3–4 septal lines), 2; Mild (P5 septal lines, reticulations, subpleural cysts, and ground glass opacities), 3; Moderate disease (grade 2 findings and traction bronchiectasis, peri-bronchovascular thickening or tracheal retraction with one-third to two-third lung involvement), or 4; Severe (grade 2 or 3 findings with more than two-third lung involvement).

(3) Pulmonary function tests (PFTs):

(A) Forced Spirometry (D 97723; Zan 300, Ober-thulba, Germany) to measure FEV1, FVC, and FEV1/FVC.

(B) Measuring total lung capacity (TLC), and residual volume (RV): using a constant-volume body ple-thysmograph (D 97723; Zan 300, Oberthulba, Germany).

(C) Diffusing capacity for carbon monoxide (DlCO): as measured by the single-breath technique (CE 0535; Zan 300, Oberthulba, Germany).PFTs per-formed and interpreted according to ATS stan-dards[11,12]and the results were expressed as a percentage of normal predicted values[13].

(4) O2saturation is measured via pulse oximetry (SpO2).

Statistical analysis

Analysis was performed using the statistical software (SPSS version 17; SPSS, Inc., Chicago, IL, USA). Data are presented as mean ± SD for continuous variables or frequency (percent-age) for categorical variables; usingv2-test to compare qualita-tive data while two-sampled unpaired t-test for quantitaqualita-tive data. P value of <0.05 was considered significant. The

corre-lation of parameters with each other was investigated by the Pearson correlation test.

Results

In this study 44 patients with ILDs were included, their demo-graphic data are illustrated inTable 1where their mean age was 45.7 years, and most of them were male (63.6%) and non smoker (59.1%) with mean SpO287.8%.Fig. 1revealed

that the most frequent HRCT pattern of the studied group was the fibrotic one including reticular and honey combing (45.5%) followed by ground glass pattern (36%) and the least frequent one was the nodular pattern (18.2%).

Table 2shows that fibrotic pattern was significantly more frequent among smokers while both ground glass and nodular ones were significantly more frequent among non smokers (P value 0.01). On measuring the degree of lung involvement, it was revealed that severe lung involvement (>75%) significantly occurred among different HRCT patterns with Pvalue = 0.007 (Table 3).

In 29 patients with severe lung involvement, lung volumes revealed that FEV1/FVC had no significant difference between fibrotic and ground glass pattern while it was significantly lower in nodular one in relation to both (P value = 0.000). FVC, TLC and RV were significantly lower in fibrotic pattern. On the other hand both TLC and RV had no significant differ-ence between ground glass and nodular patterns. With regard to gas exchange parameters, DLCO had no significant differ-ence between fibrotic and ground glass pattern; however it

Table 1 Demographic data of 44 studied patients.

Characteristics

Age (years) (mean ± SD) 45.77 ± 11.7

Sex (No & %)

 Male 28 (63.6%)

 Female 16 (36.4%)

Smoking habit (No & %)

 Smoker 18 (40.9%)

 Non smoker 26 (59.1%)

SpO2(mean ± SD) 87.8 ± 4.6

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Figure 1 HRCT pattern in 44 studied patients.

Table 2 HRCT pattern in relation to smoking status.

Smoker (18) Non smoker (26) P-value

No. % No. %

Fibrotic 14 70.0 6 30.0 .001*

Ground glass 4 25.0 12 75.0

Nodular 0 0. 8 100.0

* Significant values.

Table 3 Degree of lung involvement in relation to different HRCT pattern. Severe lung involvement (29) Mild to moderate lung involvement (15) P-value No. % No. % Fibrotic 12 60 8 40 0.007* Ground glass 9 56.2 7 43.8 Nodular 8 100 0 0. * Significant values.

Table 4 Pulmonary function parameters in relation to HRCT pattern in 29 patients with severe lung involvement.

Fibrotic (mean ± SD) Ground glass (mean ± SD) Nodular (mean ± SD) P1 P2 P3

FEV1/FVC 86.50 ± 3.61 89.44 ± 3.90 65.50 ± 2.49 0.063 0.000* 0.000

FVC 41.33 ± 6.88 55.56 ± 7.32 46.38 ± 6.36 0.000* 0.12 0.01*

TLC 41.83 ± 7.47 56.56 ± 7.45 57.88 ± 6.98 0.000* 0.000* 0.71

RV 39.42 ± 6.68 55.67 ± 7.52 58.75 ± 7.73 0.000* 0.000* 0.38

P1 (fibrotic and ground glass), P2 (fibrotic and nodular), P3 (ground glass and nodular).

* Significant P-values.

Table 5 Gas exchange parameters in relation to HRCT pattern in 29 patients with severe lung involvement.

Fibrotic (mean ± SD) Ground glass (mean ± SD) Nodular (mean ± SD) P1 P2 P3

DLCO 37.25 ± 4.63 33.89 ± 3.37 47.75 ± 6.36 0.12 0.000* 0.000*

SpO2 85.83 ± 2.58 81.89 ± 2.47 90.88 ± 2.53 0.002* 0.000* 0.00*

P1 (fibrotic and ground glass), P2 (fibrotic and nodular), P3 (ground glass and nodular).

* Significant P-values.

Table 6 Pulmonary function parameters in relation to HRCT pattern in 15 patients with mild to moderate lung involvement.

Fibrotic (mean ± SD)

Ground glass (mean ± SD) P value FEV1/ FVC 86.00 ± 4.89 85.00 ± 2.16 0.627 FVC 50.75 ± 6.23 61.29 ± 4.31 0.002* TLC 51.25 ± 7.36 64.43 ± 5.38 0.002* RV 48.50 ± 5.93 62.43 ± 5.381 0.000* * Significant values.

Table 7 Gas exchange parameters in relation to HRCT pattern in 15 patients with mild to moderate lung involvement.

Fibrotic (mean ± SD)

Ground glass (mean ± SD) P value DLCO 43.62 ± 4.95 55.1 ± 3.76 0.000* SpO2 89 ± 2.75 93.71 ± 1.60 0.002 * * Significant values.

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Table 8 Correlation between TLC and DLCO among differ-ent HRCT patterns. r P-value Fibrotic 0.991 0.000* Ground glass 0.359 0.065 Nodular 0.218 0.302 *Significant values.

Figure 2 Correlation between TLC and DLCO in 20 patients with fibrotic pattern.

Figure 3 Correlation between TLC and DLCO in 16 patients with ground glass pattern.

Table 9 Correlation between DLCO and SpO2 among

different HRCT patterns. r P-value Fibrotic 0.980 0.000* Ground glass 0.986 0.000* Nodular 0.991 0.000* * Significant values.

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was significantly lower in both of them than in nodular pattern (P value = 0.000), also SpO2was significantly higher in

nodu-lar pattern than in fibrotic and ground glass ones (P value = 0.00) as shown inTables 4 and 5.

In 15 patients with mild to moderate lung involvement; FVC, TLC and RV were significantly lower in fibrotic pattern (P value = 0.002, 0.002, and 0.000, respectively); also both DLCO and SpO2 were significantly lower in fibrotic pattern

(P value = 0.000, and 0.02, respectively) as shown inTables 6 and 7.

Table 8revealed that there was significant positive correla-tion between TLC and DLCO in fibrotic pattern (P value = 0.000) (Fig. 2) while no correlation could be detected between them in the other two patterns (Fig. 3). Moreover, there was a significant positive correlation between DLCO

and SpO2in all different patterns (P value = 0.000) as shown

inTable 9andFigs. 4–6.

Discussion

Up till now there is a debate in how much correlation occurred between radiological patterns and the pulmonary functions of ILDs patients. Many investigators have attempted to use PFTs to differentiate patterns of ILDs. The identification of a rela-tively raised residual volume in hypersensitivity pneumonitis compared with IPF was detected, which is believed to be related to small airway involvement [14]. In addition, differ-ences in gas exchange have been detected in patients with IPF appearing to have a greater reduction in DlCO in spite of correction for lung volume[15].

Figure 4 Correlation between DLCO and SpO2among 20 patients with fibrotic pattern.

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In this study, fibrotic lesions including reticular and honey-combing are the most frequent HRCT findings as it repre-sented in 45.5% of included patients. This is consistent with the result of J. Biederer and coworkers who studied 53 patients with ILDs due to rheumatoid arthritis and detected predomi-nant reticular pattern in 40 of 53 patients[16]. Seventy percent of patients with fibrotic pattern were current smokers and it may be attributed to IPF, which represent most of the fibrotic pattern in HRCT, whereas most patients with ground glass and nodular patterns were non-smokers and this may be due to non specific interstitial pneumonitis that mostly presented in collagen vascular disease and to extensive allergic alveolitis, respectively. Fibrotic and ground glass patterns exhibited restrictive dysfunction (high FEV1/FVC, and low lung vol-umes) and this is due to the affection of alveoli and interstitial compartments not related to small airways (interlobular and intralobular septal interstitium). On the other hand, nodular pattern is associated with mixed dysfunction (low FEV1/ FVC, and low lung volumes). This is attributed to the presen-tation of centrilobular nodules in subacute hypersensitivity pneumonitis with bronchiolitis plus the affection of centrilob-ular interstitium resulting in airway obstruction and this is consistent with the results of a previous study on hypersensitiv-ity pneumonitis[7].

Results of our study revealed that Lung volumes (FVC, TLC, and RV) were significantly lower in fibrotic lesion regardless to the degree of lung involvement. However DLCO among different patterns were dependent upon the degree of lung involvement. In severe lung involvement (>75 affection), severe diffusion defect (DLCO < 40%) was observed in both fibrotic and ground glass lesions, but in mild to moderate lung involvement (<75% affection), DLCO is significantly lower in fibrotic pattern than ground glass pattern which exhibited moderate diffusion defect. This is compatible with a study that demonstrated a significant negative correlation between DLCO and the degree of lung involvement[16]. Non specific interstitial pneumonia with predominant ground glass in scle-roderma exhibited mild to moderate decreased DLCO in cases of mild to moderate lung involvement which is compatible with our study [8]. Thus DLCO correlates better with the extent of disease on HRCT[17–19].

In this study, in mild to moderate lung involvement of ground glass pattern, the lung volumes (FVC, TLC, and

DLCO) were 61.29 ± 4.3, 64.43 ± 5.38, and 55.1 ± 3.76, respectively. These were comparable with an update study[9] that studied HRCT pattern and pulmonary function tests in rheumatoid arthritis patients with ILDs, and detected that the mean values for FVC, TLC, and DLCO were (60.7 ± 0.9, 70 ± 10.4, and 59.4 ± 7.2, respectively).

Our results revealed a significant positive correlation between TLC and DLCO in fibrotic pattern, while no correla-tion could be detected between them in ground glass pattern and this is consistent with another study[20] of 14 patients with fibrotic pattern of idiopathic pulmonary fibrosis, and the revealed gas transfer was correlated to lung volumes. The more affected DLCO with less affected lung volumes in ground glass pattern is indicative of pulmonary hypertension [21]that coexists with non specific interstitial pneumonia of collagen vascular diseases.

We detected a highly significant correlation of DLCO with oxygen saturation (SpO2) in different patterns and this is

explained by the occurrence of gas exchange affection with ear-lier DLCO impairment where there was a reduction of DLCO in all patterns regardless to the degree of lung involvement in all patients.

Conclusion

HRCT patterns and the degree of lung involvement of ILDs correlate with pulmonary function parameters. Lung volumes are lower in fibrotic lesion regardless degree of lung involve-ment, while DLCO among different patterns were dependent upon the degree of lung involvement. Restrictive pulmonary dysfunction correlate with gas exchange in fibrotic pattern while in ground glass one, gas exchange is independent on lung volumes.

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