Remember me
ORIGINAL ARTICLE
Year : 2021 | Volume
: 70
| Issue : 1 | Page : 135-143
Epidemiological, clinical and radiological patterns of interstitial lung diseases at cardiothoracic Minia University Hospital: a single centre prospective study
Azza F Said, Basma M Abdel-Kader, Manal F Abu-Samra, Zainab Hassan Saeed, Moustafa Abdel-Kader, Ahmed H Kasem
Department of Chest Diseases, Radiology, Faculty of Medicine, Minia University, Minia, Egypt
Correspondence Address:
MD Ahmed H Kasem
Department of Chest Diseases, Faculty of Medicine, Minia University, Minia, 61511
Egypt
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ejcdt.ejcdt_72_20
Background Interstitial lung diseases (ILDs) have undergone significant evolution in recent years. Clinical epidemiological data on ILDs from Egypt are limited. We performed this research to assess the epidemiological, clinical, and radiological patterns of ILDs at a single center for 1-year duration.
Patients and methods An observational cohort study was performed on 100 patients of ILDs. Patients’ demographic, clinical examination, spirometry, 6-min walk test, collagen profile, and high-resolution computed tomography of the chest data were collected.
Results A total of 100 patients with ILDs were studied, and 77 of them were females. The mean age of the patients was 48 years, 88% of them from rural areas, and ∼50% of them were housewives with significant exposure to bird breeding. The distribution of ILD cases was hypersensitivity pneumonitis (HP) (51%) followed by idiopathic interstitial pneumonia (26%), unclassifiable ILD (13%), and lastly, connective tissue disease associated with ILD (10%). Most of the clinical features had nearly an equal distribution among the different types of ILDs (P>0.05). Regarding radiological pattern on high-resolution computed tomography chest, it was found that ground-glass opacity was the only pattern that had a significant occurrence in patients with HP than other subtypes.
Conclusion Approximately half of the studied patients had HP, so attention to those exposed patients is an important element for early diagnosis of HP as the most common subtype of ILD.
Keywords: clinical features, hypersensitivity pneumonitis, interstitial lung disease, radiological patterns
Interstitial lung diseases (ILDs) represent a very large group of more than 200 different entities, many of which are rare or ‘orphan’ diseases. They are typically characterized by the presence of inflammation and altered lung interstitium. Specific forms of ILDs can be differentiated from one to another when clinical data, radiologic imaging, and pathologic findings (if lung biopsy is needed) are combined to reach a confident diagnosis [1].
There are few epidemiologic studies available regarding the incidence, prevalence, or relative frequency of ILDs. To date, many ILD registries have been established in various regions around the world including the institutional and hospital-based studies. Knowledge of the relative frequency of the diagnosis of the different types of ILD may provide interesting information about these diseases [2]. In addition to the relative frequencies of subtypes of ILDs, details on descriptive epidemiology, clinical, and radiological features of ILDs are required to give the real size of these diseases, especially in our locality and to help in early detection issues.
AimThis study aimed to assess the epidemiological, clinical, and radiological features of patients with ILDs who were refereed to Cardiothoracic Minia University Hospital within a 1-year duration.
Patients and methodsThis study was a prospective cohort study that included 107 patients with ILDs who were referred to the Chest Department at Cardiothoracic Minia University hospital as inpatients and or outpatients during the period between March 2017 and March 2018.
In the present study, the diagnosis of ILDs was based on a combination of clinical symptoms of ILD such as dyspnea and dry or productive cough. Physical examination revealed crepitations and clubbing in some cases, with a restrictive ventilatory defect on spirometry, and chest high-resolution computed tomography (HRCT) findings in the form of reticular changes, ground-glass, nodular shadow, honeycombing, cystic changes, mosaic, traction bronchiectasis, and mixed patterns were revealed. None of the patients was diagnosed by thoracoscopic or transbronchial lung biopsies. Exclusion criteria included patients with ILDs less than 18 years and patients with interstitial pulmonary infiltrate on chest HRCT secondary to both malignancy or postinfectious state. Seven patients were excluded from the study: two patients because of their ages were less than 18 years, four patients with known malignancies and interstitial infiltrate on HRCT (two with primary lung cancer, one with metastatic cancer and the last one was due to lung involvement secondary to lymphoma), and the last one was owing to interstitial infiltrate due to viral pneumonia. The nature of the present study was explained to all patients. A verbal consent was obtained from all patients. The study was approved by the research ethics committee of Minia Faculty of Medicine.
Clinical and laboratory assessment
All patients were subjected to history taking regarding occupational exposure to organic dust, environmental exposures, birds and animal breeding, smoking, and medications that can cause ILD. Assessment of pulmonary symptoms, its duration, grading of dyspnea, and comorbid conditions was done. Other symptoms that would be associated with ILDs such as small joint pain, morning stiffness, and cutaneous lesions were noted. Exercise capacity was assessed by a 6-min walk test (6MWT). The 6MWT was done based on American Thoracic Society Guidelines [3].
Spirometry was done using a 2130 spirometer (V max, Sensormedicus, California, USA), which was calibrated daily. Results were obtained for forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and FEV1/FVC ratio.
Radiological assessment
Chest radiograph and noncontrast chest HRCT were done for all patients. HRCT chest was done using a 16-slice multidetector CT scanner (GE Bright Speed, Milwaukee, Washington, USA). The scan was obtained at a slice thickness of 0.6–1 mm, at 120 kV, and a matrix size of 768 or the largest available. The imaging time was 1 s. The images were reconstructed with high spatial frequency for parenchymal analysis. All images were obtained at a window level appropriate for lung parenchyma (window width: 1100–1600 HU; window level: −600 to −700 HU). Expiratory HRCT scans were used in some cases with air trapping.
All images of HRCT were interpreted as the predominant pattern, extent, and distribution of lesions.
Blood samples were taken for complete blood count, and assessment of collagen profile among all patients was done.
Doppler echocardiography
It was done using conventional echocardiographic equipment (GE Vivid 3; General Electric, Chicago, USA) for evaluation of echocardiographic criteria of pulmonary hypertension [4].
According to international classification of ILDs [5], the 100 studied cases were classified into 51 cases of hypersensitivity pneumonitis (HP) and 49 cases of ILD other than HP [26 cases of idiopathic interstitial pneumonia (IIP), 10 cases of connective tissue diseases (CTD) associated ILD, and 13 cases of unclassifiable ILD].
Cases of HP were diagnosed based on a history of exposure to organic dust, like bird breeding, with HRCT findings suggestive of HP in the form of centrilobular micronodules, ground-glass opacity (GGO), and mosaic attenuation with a predominance of lesion in upper lung zones in subacute and chronic HP [6]. Five cases had acute HP as their symptoms were for less than 6 weeks, eight had subacute HP as their symptoms between 6 and 23 weeks, and 38 patients as chronic HP, and their duration of illness was more than or equal to 24 weeks [7].
Cases of IIP were diagnosed based on ATS/ERS consensus classification of IIP [8]; they were divided into eight cases of idiopathic pulmonary fibrosis (IPF), eight cases of nonspecific interstitial pneumonia, five cases of cryptogenic organizing pneumonia, three cases of desquamative interstitial pneumonia, and two cases of respiratory bronchiolitis ILD.
The diagnosis of CTD-ILD was based on ILD within the setting of well-defined CTD. CTD was diagnosed by senior doctors of the Rheumatology Department according to the American College of Rheumatology corresponding criteria [9],[10],[11],[12]: five cases of rheumatoid arthritis, three cases of scleroderma, one case of systemic lupus erythematosus, and one case of dermatomyositis.
Unclassifiable ILD was present in 13 patients, as they could not be classified with a specific form of ILD, as there was a major discrepancy between clinical and radiological findings [13].
Statistical analysis
Data were collected, verified, coded, and then analyzed using Statistical Package for Social Science, version 20 (IBM, USA). Data were presented as mean and SD for quantitative data and number and percentage for qualitative data. Independent sample t test was used for analysis of quantitative data and χ2 test for analysis of qualitative data. P values of less than 0.05 was considered as the cutoff point to determine the level of significance.
Results[Figure 1] shows the subtype distribution among the studied patients with ILD.
It was found that females, those who lived in rural areas, and housewives were significantly higher among patients of HP than those of other ILDs. Besides, nonsmokers and those who had the habit of bird breeding were seen significantly in patients with HP ([Table 1]).
[Table 2] shows the clinical features among the studied patients with ILD. The most frequent symptoms were dyspnea and cough, with no significant difference in the grading of dyspnea between those of HP and other ILD types. Chest pain, malar rash, arthralgia, and arthritis occurred in at a significant level in patients with other ILD subtypes versus patients with HP. All cases of chest pain and molar rash occurred in patients with CTD-ILD.
Regarding data of spirometry, both FVC and FEV1% predicted were significantly higher in patients with HP than other types of ILD. Analysis of the results of 6MWT revealed that no difference was found regarding 6-min walk distance (6MWD) and end test SPO2 in patients with HP and other ILDs ([Table 3]).
Table 3 Spirometry and 6-min walk test results among interstitial lung disease patientsAs shown in [Figure 2],[Figure 3],[Figure 4], the restrictive pattern is the predominant one in all subtypes of ILDs. Moreover, a combined pattern is present in five patients of HP and six patients of IIP, whereas a normal spirometry result is detected among seven and one cases of HP and IIP, respectively, with no level of significance among all subtypes of ILDs (P=0.59).
Figure 2 Pattern of spirometry in patients with ILD. ILD, interstitial lung disease.
Figure 3 (a) Axial and (b) HRCT show diffuse GGO (arrows) with areas of mosaic attenuation mainly in upper and middle lobes in a case of hypersensitivity pneumonitis. GGO, ground-glass opacity; HRCT, high-resolution computed tomography.
Figure 4 Axial HRCT images show mixed ground-glass opacities, honeycombing, and traction bronchiectasis in a patient with unclassifiable ILD. HRCT, high-resolution computed tomography; ILD, interstitial lung disease.Diverse comorbidities occur in patients with ILDs, and pulmonary hypertension was the most frequent one in both HP and the other ILDs, with only significant occurrence of obstructive sleep apnea symptoms among patients with HP (P=0.009) ([Table 4]).
[Table 5] illustrates HRCT features among the studied patients with ILDs; it was found that GGO was more frequent in patients with HP than the other types of ILDs, whereas mixed pattern was the most common pattern of abnormality among other patients with ILDs. We found also that the allocation of abnormality in the upper and middle lobe, with a central distribution of abnormality occurred significantly in patients with HP (P=0.001, P=0.005 respectively).
Table 5 High-resolution computed tomography features among the studied patients Discussion Epidemiological studies are important tools for measuring the magnitude of health problems, identifying the natural history and etiology of a disease and facilitating the formation of health care plans for disease prevention and management [14],[15]. Because various forms of ILD, such as IPF, non-IPF forms of IIP, CTD-ILD, and HP, can have similar clinical presentations, patients with suspected ILD must undergo an evaluation that adequately establishes a confident diagnosis of a specific ILD, as treatment and various management decisions are diagnosis specific and may vary considerably according to the specific form of ILD that is diagnosed [16]. So, in the current study, it was found that the most frequent diagnosis among patients of ILDs was HP (51%), followed by IIPs (26%), unclassifiable ILD (13%), and lastly, CTD-ILD (10%). Our results were near to the result of an Indian study by Singh et al. [17], which revealed that HP was found to be the most common type of ILD (47.3%), followed by CTD-ILD (13.9%) and IPF (13.7%).
Another study in Saudi Arabia found that CTD-ILD was the most frequent form of ILD (34.8%), followed by IPF (23.3%), sarcoidosis (20%), HP (6.3%), and lastly, unclassifiable ILD (1.8%) [18].
Epidemiological studies in some European countries identified different frequencies of ILD among studied patients, and sarcoidosis was the more frequent subtype [19],[20],[21].
The highest frequency of HP in the present study could be attributed to the Minia Governorate, a governorate that is surrounded by a large number of villages, and bird breeding and animal breeding are present as a frequent special habit at the countryside, and this special habit is present in 98 and 45% of the studied patients with HP, respectively. HP may develop in any environment where bacteria and fungi are present or birds and animals are kept [22].
On studying the demographic data of the studied patients with ILD, we found that most patients (52%) were in the age group of 46–60 years, with mean age of 48.4±12.8 years, with similar distributions between HP and other ILDs. However, two other studies [18],[21] found that the mean age of patients with ILD was older than that of the current study (58 and 55.4 years, respectively).
Regarding sex distribution among ILD cases, we found that females were significantly more frequent in HP cases than the other subtypes (P<0.001). Another study in Turkey found that the incidence of ILD was 24.7 per 100.000 for males and 27 per 100.000 for females [23]. In agreement with our findings [18],[24], studies have found that there is a predominance of females than males (61.2 and 60.3%, respectively). Opposite to our findings, a study in Bernalillo country, New Mexico [25], found that the prevalence of ILDs was 20% higher in males (80.9 per 100.000) than in females (67.2 per 100.000).
We found that 88% of patients were of rural descent, with a significant proportion of them among those of HP. Moreover, 68% of patients were housewives and 90% of them had HP. People living in the agricultural environment are exposed to organic dust and aerosolized particulates from a variety of sources, including feed grains, bedding, and live-stock fecal material, and they tend to have a high prevalence of lung fibrosis [26].
Never-smokers were present among 86% of ILD cases; this could be attributed to that most patients in this study were females and of rural origin, and smoking in these regions among females is usually shameful. Singh et al. [17] found 78% of patients with ILD were also never-smokers.
On analysis of the clinical characteristics of the studied patients, as expected, it was found that dyspnea and dry cough were the more frequent symptoms of ILDs, with nearly similar distribution of these symptoms and other pulmonary symptoms among patients with HP versus other ILDs. Chest pain was present significantly in CTD-ILD cases than patients with HP. Clubbing was present in 32% of patients, with a more predominance among other types of ILD (11 patients of IIP, three patients of CTD, and eight patients of unclassifiable ILD). Arthralgia, arthritis, and malar rash were significantly more in other ILD (mainly CTD-ILD) than in patients with HP.
A quantitative review of symptoms in people with progressive idiopathic fibrotic ILDs found the highest prevalence was that for breathlessness (54–98%) and cough (59–100%) [27].
Arthralgia and morning stiffness were seen among some patients with HP, besides the presence of two patients with positive anti-cyclic citrullinated peptide, and five patients had positive anti-nuclear antibodies among them. Positive ANA and Anti CCP among some patient with HP was in agreement with Cort et al. [28] study, as they adressed HP patients with autoimmune features if they had one specific CTD symptom and one serlogical test suggesting autoimmune disease.
Spirometric evaluation of the studied patients revealed a restrictive pattern in 88.2% of involved patients and combined obstructive restrictive in 9.4% of others. This mixed functional pattern was among five HP patients and four in other ILD types.
In this study, the mean values of FVC and FEV1% predicted were significantly higher in HP versus other types of ILD (P=0.04 and 0.02, respectively). The mean FVC among all studied patients of ILD was 48.7±16.4%predicted, which signifies possible severe restrictive defect. In a previous study [17], the mean FVC % predicted in all subtypes was 57.2±23.2% predicted which is higher than the mean FVC% predicted in our study.
Regarding 6MWT among the studied patients, we found that the mean 6MWD among the four types of ILD was 202.6±80.4 m and the mean end test SPO2 was 81.5±10.7%, with no significant difference between HP and the other subtypes. Previous two studies [29],[30] found a higher 6MWD and end test SPO2 than the current study. The shorter 6MWD in the present study than the other two studies may be owing to 77% of the studied patients were females, and their mean FVC was 48.7±16.4% predicted, which denoted severe restrictive defect. Adding to this, 69% of patients with ILD had echocardiographic diagnosis of pulmonary hypertension which also reduces 6MWD. In general, men have a higher 6MWD than women. One plausible explanation is that muscle mass and therefore maximum leg-muscle force is lower in women than men [31]. The better the resting spirometric data were, the greater the 6MWD. Significant correlations were also observed between 6MWD and FEV1, or FVC [32].
Regarding comorbidities in the studied patients, we found that pulmonary hypertension, gastroesophageal reflux symptoms, systemic hypertension, and diabetes mellitus were the most frequent ones in ILD (69, 42, 32, and 20%, respectively) whereas symptoms of obstructive sleep apnea occurred significantly among patients with HP. Previous studies found that the various comorbidities of ILDs are more frequently observed in patients with IPF as this may affect the prognosis of these patients.
Radiological evaluation through HRCT has become increasingly essential to the characterization and classification of ILD. We found that there was a different CT patterns among the studied patient with no significant difference in these patterns among HP and other ILD cases except GGO which occurred significantly in patients of HP (50.9 vs. 30.6%, P=0.04). In a retrospective study on HP in Brazil, GGO was the most frequently found, as it presented in 71.7% of patients, centrilobular-nodules were found in 67.4%, and findings of fibrosis as reticulation were present in 65% of patients [33].
Unfortunately, mixed pattern was the most encountered in our study in other types of ILD, and no specific pattern characterized any form of different types of ILD.
The present study has some limitations. The first of these limitations is nonperformance of invasive procedures like transbronchial lung biopsy or bronchoalveolar lavage especially in cases of unclassifiable ILD. Second, there were no data on the outcome of these patients during the duration of the study regarding frequency, severity of exacerbations, and hospitalization. Lastly, the duration of the study was short.
ConclusionIn conclusion, HP is the most frequent subtype encountered in our study; the mean age of patients with ILD is 48 years; the disease occurs more in females of rural descent, in housewives, and with bird breeding, especially in HP; and never-smokers represent the majority of patients. There is nearly an equal frequency of clinical features among patients of HP and other types of ILDs, except the significant presence of clubbing and other extrapulmonary symptoms in patients of other ILDs. Except for the presence of GGO and centrilobular distribution of abnormality in HRCT among patients of HP, no other pattern or extent of abnormality represented a difference between HP and other ILDs subtypes. Further studies addressing the disease pattern are needed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
Comments (0)