Professor

Department of Respiratory Medicine

Topiwala National Medical College

B Y L Nair Hospital

Mumbai, 400008

India

Address for correspondence

Dr J M Joshi.

Professor,

Department of Respiratory Medicine,

Topiwala National Medical College,

B Y L Nair Hospital,

Mumbai, 400008

India.

Pulmonary hypertension (HT) and cor pulmonale is an important complication of chronic respiratory disorders. This study was a retrospective analysis to evaluate obliterative bronchiolitis- (OB) as a cause of pulmonary HT and cor pulmonale. Cases with chronic respiratory symptoms with clinical, radiographic or electrocardiograph (ECG) evidence of pulmonary HT, that was confirmed by Two-dimensional echocardiography (2 D ECHO) with continuous and pulsed wave Doppler studies, were included. A detailed evaluation was done to establish the etiology, which included history, physical examination, chest radiography, spirometry, arterial blood gas (ABG) analysis, high resolution computed tomography (HRCT) with expiratory scans, ventilation perfusion scans, sleep studies and lung biopsy as required. OB was diagnosed in presence of chronic airflow limitation forced expiratory volume (FEV1) < 60% of predicted, in the absence of asthma, chronic bronchitis, emphysema or other causes of chronic airflow limitation and HRCT showing mosaic attenuation with exaggeration on expiratory scans. Out the total cases (n=70) there were 43 males and 27 females, age range 17-71years, mean age 41.45 years. Chronic airways diseases (CAD), 43/70, 61.4%of the total cases were the commonest causes identified for pulmonary HT and cor pulmonale. These included chronic obstructive pulmonary disease –COPD (n=18), 25% of the total cases and postinfectious obliterative bronchiolitis-OB (n=16), 22.85% of the total cases. Bronchiectasis (n=7) bysinossiss (n=1) and allergic bronchopulmonary aspergillosis-ABPA (n=1) were the other CAD causing pulmonary HT. COPD was exclusively seen exclusively in the elderly, while OB was seen in a younger age group. Interstitial lung disease ILD (n=13), kyphoscoliosis (n=2), primary pulmonary HT (n=3), chronic lung fibrosis secondary to tuberculosis (n=6), obesity hypoventilation syndrome-OHS (n=1), pulmonary HT associated with portal HT (n=1) and pleural fibrosis (n=1) were the other causes noted. OB is an important cause for pulmonary HT and cor pulmonale and HRCT with expiratory scans should be included in the diagnostic algorithm of pulmonary HT.

INTRODUCTION

Chronic airway disease (CAD) with chronic airflow limitation, of which COPD is the best known, is a common cause of pulmonary HT¹. COPD is a clinical descriptive term for patients mostly elderly, who has airflow obstruction that is not completely relieved by therapy⁵ and is related to tobacco smoking in 80-90% cases⁶. Obliterative bronchiolitis (OB) also called constrictive bronchiolitis (CB), is a disorder caused by obstruction of the small airways is another important cause of CAD resulting in chronic airflow limitation. The functional abnormality is obstructive and can be misdiagnosed as COPD. OB is not diagnosed very often, perhaps because of the uncritical use of the term "chronic obstructive pulmonary/lung disease". ⁸ However, HRCT findings of heterogenicity of lung density ("mosaic" pattern) with exaggeration on expiration is diagnostic in the correct clinical context.⁹

A retrospective analysis of cases of pulmonary HT and cor pulmonale, diagnosed non-invasively by ECHO with Doppler studies was made to identify the OB as a cause of pulmonary HT and cor pulmonale in adult patients.

MATERIAL AND METHOD

This study was a retrospective analysis of 70 consecutive adult patients suffering from pulmonary hypertension (HT) and cor pulmonale, seen in the out patients department of a tertiary care hospital. Cases with chronic respiratory symptoms with clinical, radiographic or electrocardiograph (ECG) evidence of pulmonary HT, that was confirmed by two-dimensional echocardiography (2 D ECHO) with continuous and pulsed wave Doppler studies, were included. Radiographic assessment of pulmonary artery diameter, electrocardiography and M-mode ECHO have a high specificity for detection of pulmonary HT.³ Recently tricuspid incompetence (TI) gradient measured by continuous wave Doppler has been used as a marker of pulmonary HT⁴. This estimation corresponds well to pressures measured by right heart catheterisation and the error limits for Doppler derived pressure calculations are only 5-9 mm/Hg⁴. In chronic obstructive pulmonary disease (COPD), where it is difficult to recover a TI signal of significant quality, pulsed wave Doppler can detect pulmonary HT in over 90% cases¹, although precise calculation of pulmonary artery pressure is poor.

All patients were subjected to a detailed clinical examination, chest radiography, spirometry, arterial blood gas analysis (ABG), before and after exercise, and high resolution computed tomography (HRCT). Additional tests like total and specific immunoglobulin E (IgE), sweat chloride levels, electron microscopy of nasal mucosa, ventilation perfusion scan; expiratory HRCT, sleep studies and lung biopsy were performed, as required to establish the etiology in each case. The criteria used for diagnosis of OB were as suggested by Turton et al ⁸ i.e. presence of chronic airflow obstruction, forced expiratory volume (FEV1) in 1 second <60% and exclusion of other causes of airflow obstruction like asthma, emphysema or any other causes. Characteristic HRCT pattern of mosaic attenuation with exaggeration on expiration is diagnostic in the correct clinical context. ⁹ Further, to establish the etiology of OB, history of exposure to inhaled toxins, or ingestion of drugs like pencillamine, a history suggestive of connective tissue disorders and history severe respiratory infections prior to onset of symptoms was obtained.

RESULTS

Out the total cases (n=70) there were 43 males and 27 females, age range 17-71years, mean age 41.45 years. Table 1 shows the common causes of pulmonary HT and cor pulmonale seen in this study. Chronic airways diseases (CAD), 43/70, 61.4%of the total cases were the commonest causes identified. Interstitial lung disease (ILD) 13/70, 18.5 % cases were another major cause identified. The common CAD causing pulmonary HT were Chronic obstructive pulmonary disease –COPD (18/43, 41.9%), postinfectious obliterative bronchiolitis-OB (16/43, 37%), and bronchiectasis (7/43, 16%). Bysinosis and allergic bronchopulmonary aspergillosis-ABPA one case each were two other causes in the CAD group. Comparative data of the major causes of pulmonary in this study is shown in table 3. COPD was exclusively seen in the older age group, age range 40-71years, mean age 50.5 years, while OB was seen in younger age group, age range 21-58 years with a mean age of 38.5 years. The profile of cases of OB is shown in Table 2. History of respiratory infections prior to the onset of symptoms suggested post-infectious OB in most cases. Chronic lung fibrosis secondary to tuberculosis, kyphoscoliosis and primary pulmonary HT and obesity hypoventilation syndrome (OHS) were the other etiologies for pulmonary HT.

Comparative data of the major causes of pulmonary HT in the present study is shown in table 3. Pulmonary HT due COPD was seen in the elderly, age range 40-71 years, mean age 50.5 years. Pulmonary HT due to OB (table 4) was seen in a much younger age group, age range 21-58 years, mean age of 38.5 years, more commonly in females and the duration of symptoms was 1-30 years. Only 2 of these cases had history of smoking, one smoked occasionally and the other was an ex smoker. One case each gave history of diabetes mellitus and systemic hypertension, but left ventricular abnormality was not seen in both cases on ECHO study. One case had euthyroid goitre but there was no clinical or flow volume loop abnormality of upper airway obstruction. Two cases had been subjected to pneumonectomy in the past, with the diagnosis of bronchiectasis without the benefit of HRCT. All cases had severe airflow limitation and hypoxaemia with hypercapnoea on ABG. History of severe childhood respiratory suggested postinfectious OB in 50% cases whereas absence of any specific etiology suggested idiopathic OB in the rest.

DISCUSSION

Pulmonary hypertension is difficult to diagnose because the symptoms – fatigue, dyspnoea, syncope, and signs – a loud pulmonary second sound, with or without tricuspid regurgitation are vague and common to many diseases. ² Pulmonary HT therefore, should be suspected in patients with persistent hypoxaemia, who complain of deteriorating exercise tolerance with stable lung functions or in those who develop fluid retention¹. Pulmonary hypertension (HT) secondary to chronic respiratory disorders and cor pulmonale are usually caused by ¹ chronic hypoxic lung disease including chronic airflow obstruction, fibrosing lung disease and ventilatory failure due to primary chest wall dysfunction, thromboembolic pulmonary disease and connective tissue diseases.

The results of this study suggest that chronic airway disease (CAD) is the most frequent cause for pulmonary HT and cor pulmonale. OB (22.85%) of the total cases was found to be the commonest cause after COPD (25%) of the total cases. Whereas COPD was seen exclusively in the older age group, OB caused pulmonary HT and cor pulmonale in a relatively younger age group.

The small airways (bronchioles) are the airways less than 2 mms in diameter and are called the "silent zone" of the lungs as they offer very little resistance to airflow. A large number of small airways have to be affected before they produce symptoms and pulmonary function abnormality. OB is a disorder caused by partial or complete obstruction of the small airways (bronchi and bronchioles) that occurs following an insult to the lower respiratory tract, ⁷ which may be viral or mycoplasma infections, collagen vascular disorders, inhaled toxins, drugs, graft versus host reaction. Sometimes OB may be idiopathic. Post infectious OB is associated with bronchiectasis, persistent atelectasis and hyperlucent lung syndrome.

The diagnosis of OB should be considered in presence of chronic airflow limitation, after exclusion of emphysema, chronic bronchitis or any other known cause of airway obstruction⁸. Radiographic features of OB are non specific but HRCT findings of heterogenicity of lung density that creates a "mosaic" pattern with exaggeration on expiratory scan is diagnostic in the correct clinical context.⁹ The pattern of mosaic attenuation is due to small airway obstruction (bronchiolar obstruction). This abnormality is seen in several CAD such as asthma, emphysema and bronchiectasis. Hence the diagnosis of OB is one of exclusion. COPD is seen almost exclusively in smokers and is easy to diagnosis due to associated changes of centiacinar emphysema on HRCT. Asthma is seen in atopic individuals, and is associated with elevated serum IgE.

However it is sometimes difficult to make a distinction between post infectious OB which is associated with areas of bronchiectasis, and bronchiectasis with mosaic pattern due to the associated small airway disease. In the present study we have included cases of chronic bronchial suppuration as bronchiectasis irrespective of mosaic attenuation. It is interesting to note that 4/7 patients of bronchiectasis, in the present study had mosaic attenuation due to small disease. In a study by Hansell et al, it was found that such changes are common and the authors suggested that in these cases, OB might have been an early event in the pathogenesis. However, bronchiectasis though less frequently seen in the developed world due to control of childhood infections, is frequently seen in the less developed countries. In most cases childhood respiratory infections cause either bronchiectasis or OB, however in some individuals both bronchiectasis and OB may result. In these i.e. OB alone and bronchiectasis with OB, greater airflow limitation due to small airway obstruction perhaps causes early pulmonary HT and cor pulmonale.

In conclusion, OB may be an important cause for pulmonary HT and cor pulmonale, particularly in the young adults. OB should be suspected in case of chronic airway disease with airflow limitation, and HRCT with expiratory scans should be included in the diagnostic algorithm of pulmonary HT.

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CAD = chronic airway disease

COPD= chronic obstructive pulmonary disease,

OB= obliterative bronchiolitis,

ILD= interstitial lung disease,

PPH= primary pulmonary hypertension

ABPA = allergic bronchopulmonary aspergillosis,

OHS =obesity hypoventilation syndrome.

Total cases=16

Age range =21-58 years

Mean age =38.5 years

Smoking history=2 (one ex- smoker and one occasional smoker)

M: F= 5:11

History of serious childhood respiratory infections=8

Duration of illness = 1-30 years

Associated disorders: hypertension=1, diabetes mellitus=1, pneumonectomy=1,

Euthyroid goitre without upper airway obstruction=1