|
 
 |
| ORIGINAL ARTICLE |
|
| Year : 2023 | Volume
: 3
| Issue : 2 | Page : 56-63 |
|
Profile of pulmonary hypertension in patients presenting with respiratory symptoms at a tertiary care hospital in Mumbai
Ketaki Utpat, MK Kanmani, Vinod Pal, Unnati Desai, Jyotsna M Joshi
Department of Pulmonary Medicine, TNMC and BYL Nair Hospital, Mumbai, Maharashtra, India
| Date of Submission | 19-Aug-2022 |
| Date of Acceptance | 10-Oct-2022 |
| Date of Web Publication | 02-May-2023 |
Correspondence Address:
Dr. Unnati Desai
Department of Pulmonary Medicine, TNMC and BYL Nair Hospital, Mumbai, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jalh.jalh_27_22
Background: Pulmonary hypertension (PH) is a disorder of the pulmonary vasculature caused due to vasoconstriction, vaso-destruction, or vaso-obliteration as a complication of a varied spectrum of diseases referred to a pulmonologist. We conducted this study to contemplate the profile of PH in a tertiary care hospital in Mumbai. Methodology: This was an observational study undertaken in the department of pulmonary medicine at a tertiary care center after internal ethical committee approval. Patients with respiratory symptoms referred to us with PH as estimated pulmonary artery systolic pressure (PASP) of ≥40 mmHg by transthoracic two-dimensional echocardiography (corresponding to mean pulmonary artery pressure of ≥25 mmHg) were included in the study. The profile of these patients was studied on basis of parameters such as demography, etiology, symptomatology, radiological features, 6-min walk distance (6-MWD), and spirometry. Data were analyzed using Microsoft Excel software. Results: Among 347 patients, 54% were men. Majority of the patients (53.5%) were aged between 45 and 65 years. The most common symptom was dyspnea (86%). The most common examination finding was loud pulmonary component of second heart sound (62%). The common etiologies of PH were postinfectious obliterative bronchiolitis (OB) 30%, interstitial lung diseases 26%, chronic obstructive pulmonary disease 24%, and obstructive sleep apnea 14%. There was a negative correlation between 6-MWD, forced vital capacity % predicted, forced expiratory volume in 1st s % predicted, and PASP. Conclusion: Airway disease is the most common etiology of PH in patients presenting to a pulmonologist in India, out of which postinfectious OB forms the major bulk.
Keywords: Obliterative bronchiolitis, pulmonary artery systolic pressure, pulmonary hypertension
How to cite this article:
Utpat K, Kanmani M K, Pal V, Desai U, Joshi JM. Profile of pulmonary hypertension in patients presenting with respiratory symptoms at a tertiary care hospital in Mumbai. J Adv Lung Health 2023;3:56-63 |
How to cite this URL:
Utpat K, Kanmani M K, Pal V, Desai U, Joshi JM. Profile of pulmonary hypertension in patients presenting with respiratory symptoms at a tertiary care hospital in Mumbai. J Adv Lung Health [serial online] 2023 [cited 2023 May 28];3:56-63. Available from: https://www.jalh.org//text.asp?2023/3/2/56/375534 |
| Introduction | |  |
Pulmonary hypertension (PH) is a disease state characterized by persistent elevation of pulmonary vascular resistance.[1] PH can exist as isolated pulmonary vasculopathy without an identifiable cause in which case it is termed as pulmonary arterial hypertension (PAH). Although PH is a clinical entity, it has got both hemodynamic and pathological aspects. It is defined hemodynamically as persistent elevation of mean pulmonary artery pressure (PAP) of >25 mmHg at rest, measured by right heart catheterization.[2] The definition of PH as mean PAP >30 mmHg on exercise has been abandoned in view of lack of supporting evidence and fact that normal individuals can reach much higher values on exercise.[3],[4] The PAP can be gauged noninvasively by transthoracic two-dimensional (2D) Doppler echocardiography (ECHO) by estimating tricuspid regurgitation jet velocity using modified Bernoulli equation.[5] The estimated pulmonary artery systolic pressure (PASP) by transthoracic ECHO has a good correlation with invasively measured mean PAPs.[6] The error of calculation is of tune of only 5–9 mmHg.[7] Overestimation of pulmonary pressure may occur; however, Doppler ECHO has a good negative predictive value.[8] Uncontrolled PH progresses into cor pulmonale and later with decompensation of right ventricular function leads to right heart failure (RHF). The level of PH associated with chronic respiratory disorders typically is relatively mild.[9] The mean PAP in patients with PH due to lung disorders is relatively lower than in patients with PAH. However, PH due to lung disorders may show right ventricular decompensation and right ventricular pump failure underlining the fact that it is the severity of underlying disease that determines the clinical symptomatology.[10] The clinical symptoms of PH in respiratory diseases are difficult to be picked up as there is a significant overlap with the symptomatology of primary disease. Most of the understanding regarding PH is centered around PAH while studies involving PH due to hypoxia or due to lung disorders are sparse. This study was conducted in a tertiary care setting caring for patients with respiratory disorders with an endeavor to study the clinical profile of patients with PH in association with respiratory disorders; There are very few studies of similar kind in the Indian settling.
| Methodology | | |
This was a prospective observational study undertaken in the department of pulmonary medicine at a tertiary care center. The study was conducted after internal ethical committee approval. PH was defined as estimated PASP of ≥40 mmHg by transthoracic 2D ECHO corresponding to mean PAP of ≥25 mmHg. PASP was calculated from tricuspid regurgitation jet using modified Bernoulli equation. Consecutive patients presenting with respiratory symptoms and already diagnosed to have PH were included in the study after informed consent. Echocardiographic evaluation was done in stable state and at least 4 weeks after an exacerbation or RHF. A detailed history was taken to note cardinal symptoms such as dyspnea, fatigue, chest pain, syncope, and edema feet. Comorbidities and addictions were noted. All patients were subjected to a detailed general examination and respiratory and cardiovascular system examination. Loud or accentuated pulmonary component of second heart sound (p2), systolic murmur, parasternal heave, hepatojugular reflux, and raised jugular venous pressure (JVP) was noted. Baseline investigations including complete blood count, liver function tests, renal function tests, arterial blood gas analysis to note the partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2), testing for human immunodeficiency virus, and thyroid function tests were obtained. Other tests performed were chest radiograph (CXR) posteroanterior (PA) view, spirometry, and high-resolution computed tomography (HRCT) of the chest. Additional tests such as total and specific immunoglobulin E, ventilation-perfusion scan, sleep studies, and transbronchial lung biopsy (TBLB) were performed, as required to establish the etiology in each case. Detailed physical examination was done. Further detailed etiological evaluation was done according to the American College of Cardiology Foundation Task Force/American Heart Association 2009 Expert consensus document on PH recommendation for diagnostic evaluation of PH. Exercise capacity was assessed by 6-min walk test (6-MWT). 6-MWT was carried out according to the American Thoracic Society guidelines for 6-MWT.[11] The patients were subjected to spirometry to document the ratio of forced expiratory volume in 1st s (FEV1) to forced vital capacity (FVC) and the absolute values and percentage predicted values of FEV1 and FVC. The data were collected and further stratified according to etiology. Statistical analysis was by percentile analysis and Pearson's correlation. Further, all the subjects were offered standard therapy according to the etiology extant at the time.
| Results | | |
The study included a total of 347 patients who presented to our outpatient department with respiratory symptoms and who met the diagnostic criteria of PH by transthoracic ECHO. The age group of patients ranged from 14 to 84 years. The mean age was 53.76 with a standard deviation (SD) of 13.20. There were 187 men and 160 women in our study accounting for 54% and 46%, respectively. The ratio of men and women was 1.2:1 [Table 1] and Diagram 1]. Of the 347 patients, 134 (38.6%) had tobacco smoking history; among the smokers, all were men [Table 1] and [Diagram 2]. The composition of clinical classes according to the WHO 2013 classification of PH in our study was as follows: clinical Class 1 had 11 patients accounting for 3.2%, Class 2 had 0 patients, Class 3 had 328 (94.5%) patients, Class 4 had only 1 (0.3%) patient, and clinical Class 5 contained 7 (2%) patients. Of the 328 patients in Class 3 PH, i.e., PH secondary to pulmonary cause, 103 (31.4%) had obliterative bronchiolitis (OB), 91 (27.7%) had interstitial lung disease (ILD) with 21 (23.07%) patients who underwent TBLB in which histopathology suggested nonspecific interstitial pneumonitis in 17 (18.68%) patients and noncaseating granuloma consistent with sarcoidosis in 4 (4.44%) patient, 83 (25.3%) had chronic obstructive pulmonary disease (COPD), and 51 (15.5%) had sleep-disordered breathing. Major causes of OB in our patients were postinfectious causes in 91 patients (88.3%), idiopathic in 7 patients (7%), and connective tissue disease (CTD)-related in 5 patients (4.85%) [Table 2]. Most common post infectious cause is past treated pulmonary tuberculosis (TB), as seen in 60 patients (66%), followed by viral exanthema-related childhood pneumonia in 25 patients (27.5%), and bacterial pneumonia as seen in 6 patients (6.5%) [Figure 1]. The mean duration of symptoms was 6.2 years with a SD of 5.6 years. [Table 1] depicts the baseline characteristics of our study group. The longest duration of symptoms at the time of diagnosis was 40 years and the shortest duration was 6 months. The main symptoms at the diagnosis [Figure 2] were dyspnea in 300 patients (86.4%), cough in 269 (77.5%), pedal edema in 58 (17%), and hemoptysis in 26 patients (7.5%). Chest pain and syncope were present in only 10 (2.9%) and 7 (2%), respectively. Loud pulmonary component of the second heart sound (p2) was the most common physical examination finding and was present in 216 (62%) of the patients. Systolic murmur was heard in 48 (14%) patients, JVP was raised in 128 (37%) patients, parasternal heave was present in 44 patients (13%), and hepatojugular reflex was seen in 152 patients (44%). Two hundred and forty-seven (72%) patients showed arterial oxygen desaturation >4 mmHg on pulse oximetry immediately following 6-MWT. CXR PA view was abnormal in overall 312 (90%) patients [Figure 3]. Of these, 250 (80%) patients had parenchymal abnormalities and 62 (20%) patients had changes associated with cardiovascular abnormalities. Of the patients with parenchymal changes, 61% had fibrotic opacities, 37% had reticulonodular opacities, and 20% had bronchiectatic changes. Cardiomegaly was found in 56 (16%) patients and pulmonary artery dilation was found in 27 (8%) patients. Electrocardiographic (ECG) changes were present in 243 (70%), while in the remaining cases, ECG was recorded as within normal tracing [Figure 4]. Right axis deviation (RAD) was seen in 232 patients (67%), right bundle branch block (RBBB) was seen in 167 patients (48%), P pulmonale was seen in 120 patients (35%), and T wave inversion was seen in 72 patients (21%). The mean 6-min walk distance (6-MWD) was 280 m with a SD of 101.8 m. The largest values of 6-MWD were seen in clinical Class 1 (PAH) (mean 6-MWD of 326 m). In Class 3 and Class 5, the mean 6-MWD was 279 m and 265 m, respectively. [Table 3] shows the division of our patients based on the WHO classes of PH. On univariate analysis, there was a statistically significant negative correlation between 6-MWD and systolic PAP, r = −0.35 (P < 0.001), i.e., as pulmonary pressures increased, 6-MWD decreased, even though this was not linear. FEV1% predicted and PaO2 had a positive statistical correlation with 6-MWD on univariate analysis (r = 0.23 and r = 0.39, respectively). PaCO2 levels had a negative correlation with 6-min walk distance (r = −0.10). [Table 4] and [Figure 5] depict a correlation analysis between 6-MWD and other variables. In our study, the mean PASP was 49.88 mmHg with a SD of 11.2 mmHg. The largest levels of PH were observed in clinical Class 1, that is, in patients with PAH. The mean PASP in Class 1 was 60.8 mmHg (30.2); in Class 3, the mean SAP was 49.3 mmHg (SD: 12.1); in Class 4, the mean PASP was 55 mmHg (SD: 0), and in Class 5, the mean PASP was 54.5 mmHg (SD: 17.1). There was a weakly negative correlation between FVC% predicted, FEV1% predicted, and the PASP, with Pearson's correlation coefficient (r) being −0.12 and −0.07, respectively. This was statistically insignificant (P > 0.05). This correlation was however significant between PaO2 values and the PASP, with Pearson's correlation coefficient (r) being − 0.77, implying that as PASP rises, PaO2 decreases, although this relationship was not linear (P < 0.001). This is depicted in [Table 5] and [Figure 5]. There was echocardiographic evidence of dilatation of chambers of right heart in 210 (60.5%) while 142 patients (41%) had a history of RHF in the past. The mean age for patients with cor pulmonale was 58.2 (±6.2) years as compared to 44.6 (±3.8) of patients without cor pulmonale. The mean duration of symptoms in patients with cor pulmonale was 110.4 months with a SD of 90.4 as compared to patients without cor pulmonale in who mean duration of symptoms was 60.8 months with a SD of 28.2 months. | Figure 3: CXR changes in our patients. CXR: Chest radiograph, PA: Posteroanterior
Click here to view |
 | Table 3: WHO classification of pulmonary hypertension in our study group
Click here to view |
 | Figure 5: Correlation analysis. PASP: Pulmonary arterial systolic pressure, PaO2: Partial pressure of oxygen, 6MWD: Six-minute walk distance
Click here to view |
 | Table 5: Correlation between pulmonary arterial systolic pressure and other variables
Click here to view |
| Discussion | | |
Our study is an observational study of clinical profile of patients with PH carried out in a tertiary care center which included 347 consecutive patients with respiratory symptoms and detected to have PH where men outnumbered women. In French registry[12] data, women formed 65.3% in overall cases, whereas in Swiss registry data, women formed 59% of the study population.[13] This difference in sexes in our study group could be due to bias in seeking medical care and the absence of tobacco smoking in women. In Indian registry data for PH carried out at a single center, it was found that the sex ratio was almost equal.[14] In Swiss registry data,[13] the median age for men was 63 years and for women was 59 years. In comparison to it, there was no significant age difference in men and women in our study. The symptoms in PH result from inadequate perfusion to an increased demand as a result of reduced cardiac output or an inability to increase the same in the face of increased demands. They include breathlessness, fatigue, chest pain, and syncope. In PAH, the symptoms rarely occur at low PASP in the presence of maintained cardiac output and when present signify the advanced nature of the disease. However, in patients with PH due to chronic lung diseases and hypoxemia, the underlying disease symptomatology predominates and it is often difficult to estimate the contribution of PH to the symptoms. Moreover, unexplained worsening of symptoms in the presence of chronic respiratory disorder may suggest the development of PH. In our study, the mean duration of symptoms was 6.2 years with a SD of 5.6 years. The main symptoms at the diagnosis were dyspnea in 85.8% and cough in 77.5%. Pedal edema, hemoptysis, chest pain, and syncope were present in a minority which is in concordance to other studies. In a national prospective study, Rich et al.[15] reported common symptoms in PH were dyspnea (60%), fatigue (73%), chest pain (47%), syncope (36%) and edema feet (37%). Respiratory examination revealed an abnormality in all except 21 cases. The findings included crackles, rhonchi, reduced breath sounds, and bronchial breath sounds. Cardiovascular examination findings associated with PH included loud p2, systolic murmur, parasternal heave, hepatojugular reflex, and raised JVP. Loud p2 was the most common physical examination finding and was present in 216 (62%) patients. Fifty-eight (17%) patients had pedal edema despite the absence of RHF and it could be attributed to PH stand alone. In a study conducted by Julian Sleeper et al., it was found that accentuated p2 was present in all cases of PH and parasternal heave was present in 93% of cases.[16] The physical examination findings for evidence of PH are highly specificity but lack sensitivity and are affected by the underlying lung diseases. The CXR findings that are associated with PH include main and hilar pulmonary arterial dilation (hilar-thoracic ratio >0.44), a transverse diameter of right descending pulmonary artery ≥17 mm on frontal CXR and cardiomegaly (cardio-thoracic ratio >0.5). In our study, CXR was found abnormal in 212 (90%) cases with PH. Of these, 250 (80%) patients had parenchymal abnormalities while the remaining 62 (20%) patients had changes associated with cardiovascular abnormalities. According to S Algeo et al., the most sensitive parameter was enlargement of main pulmonary artery with a sensitivity of 62% at high levels of PH. For mild PH, they found a sensitivity of <33% for CXR changes in detection of PH.[17] PH itself is not associated with any of the ECG changes. It is the associated right atrial and ventricular structural and functional changes that lead to changes on ECG. In our study, ECG changes were present in 243 (70%). The ECG abnormalities included RAD, P pulmonale, and T wave inversion in chest leads (V1-V4). T wave inversion in inferior leads (II, III, and augmented vector foot (AVF)), R: S >1 in V1, and RBBB. Despite low sensitivity, ECG was a good diagnostic aid in identifying patients with PH. When present, the ECG changes are markers of right atrial and ventricular load and dysfunction and advanced nature of the disease. In a study conducted by Flowers and Horan for ECG changes in cases with autopsy-proven right ventricular hypertrophy, they found that the sensitivity of ECG changes in detecting PH was low (<30%) however had high specificity.[18] In a study conducted by Bossone et al., it was concluded that ECG changes reflected right ventricular functional and anatomical abnormality and predicted poor survival.[19]
The 6-MWT is a simple, reproducible, and easy-to-perform test. It evaluates the overall and integrated response of all the systems involved in the performance of aerobic exercise. Our average 6-MWD was 280 m with a SD of 101.8 m. It had a weakly negative correlation with PASP (r = −0.35). It had a positive correlation with predicted FEV1%, predicted FVC% (r = 0.23 and 0.24, respectively), and PaO2 (r = 0.39). The 6-MWD had an inverse relation with PaCO2 (r = −0.10). Two hundred and forty-seven (71%) patients showed arterial oxygen desaturation >4 mmHg on pulse oximetry immediately following 6-MWT. Thus, the limitation in functional capacity as determined by 6-MWD in our study was affected by the underlying disease process and the advanced nature of the disease instead of levels of PH. In our study, we found a negative correlation between 6-MWD and level of PH (r = −0.35), implying that as PASP increases, 6-MWD decreases. In a study by Miyamato et al, the 6-MWD reduced in patients with PH as compared to healthy subjects. Further, the same authors found that 6-MWD <332 m was associated with poor outcome and it predicted the mortality.[20] Sims et al., from their study of COPD patients, concluded that higher PASP was associated with a decrease in 6-MWD; they found a reduction in distance walked of 6 m for every 3 mmHg rise in PAP.[21] Paciocco et al. in a study concluded that there was a 27% increase in risk of death for each per cent decrease in SaO2 after adjusting for pulmonary vascular resistance.[22] The mean PASP in our study was 49.8 mmHg with a SD of 13.2 mmHg. Further, according to different clinical classes of PH, there was a difference in PASP. The largest levels of PH were observed in clinical Class 1; patients in Class 3 had mild-to-moderate levels of PASP. The only parameter that had a significant statistical correlation with PASP was PaO2 level (r = −0.77). We did not find a statistically significant correlation between PaCO2 (r = 0.21), FVC (% predicted) (r = −0.12), and FEV1% predicted (r = −0.06). In a study by Nakamura et al., in 41 patients with chronic emphysema, a significant correlation was found between right heart catheter-measured mean PAP and hemoglobin levels and PaO2.[23]
Oswald-Mammosser et al. reported an inverse relation between PH and FEV1.[24] There was echocardiographic evidence of dilatation of chambers of right heart in 210 (60.5%) while 142 patients (41%) had a history of RHF in the past. The mean duration of symptoms in patients with cor pulmonale was 110.4 months with a SD of 90.4 months as compared to patients without cor pulmonale in who mean duration of symptoms was 60.8 months with a SD of 28 months. In patients with previous RHF, the mean duration of symptoms was 180.00 months as compared to 84.31 months in those without past RHF, implying that the duration of symptoms was a major factor that was associated with cor pulmonale and RHF. Low PaO2 and raised PaCO2 were associated with right ventricular dysfunction. Further, PaO2 had a positive correlation with FVC and FEV1 in comparison, and PaCO2 had a significant negative correlation with FVC and FEV1. Thus, patients with Right ventricular systolic dysfunction (RVD) tended to have low lung volumes which suggested an advanced disease state or respiratory failure. Campbell and Short suggested that edema formation in COPD patients was present even in the absence of RHF.[25] The composition of clinical classes according to the WHO 2013[26] classification of PH in our study was as follows: clinical Class 1 had 2 patients accounting for 3.2%, Class 2 had 0 patients, Class 3 had 328 (94.5%) patients, Class 4 had only 1 (0.3%) patient, and clinical Class 5 contained 7 (2%) patients. Thus, chronic lung diseases were the most common group of cases presenting us with PH. This was due because our study included patients with respiratory symptoms essentially presenting to us. In an Indian registry for PH of the 57 patients, 72% had PAH, 5% had left heart disease, only 7% had chronic lung disease or hypoxemia, and the remaining 16% had Chronic thromboembolic pulmonary hypertension (CTEPH).[14] In a study by Joshi, OB was the second most common (22.85%) chronic airway disease associated with PH after COPD.[27] Chronic hypoxia is the fundamental element responsible for the denouement of PH in patients secondary to chronic respiratory disorders such as obstructive airway diseases, fibrosing lung disease and ventilatory failure due to primary chest wall dysfunction, thromboembolic pulmonary disease, and CTDs. In our study, OB was the most common cause of PH. We diagnosed OB based on the criteria given by Turton et al.,[28] i.e., presence of chronic airflow obstruction, FEV1 <60%, and exclusion of other causes of airflow obstruction such as asthma, emphysema, or any other causes. The hallmark HRCT pattern of mosaic attenuation with exaggeration on expiration is diagnostic in the correct clinical context. To dig into the etiology of OB, history of respiratory infections prior to onset of symptoms, history of exposure to inhaled toxins, or ingestion of drugs such as penicillamine and history suggestive of connective tissue disorders was obtained. Moreover, we unearthed that post-TB OB (who had a history of TB) was the most common cause of OB in our patients. In another study done by Joshi,[29] it was stated that the incidence of OB could be much more than reported as these cases are frequently misdiagnosed as other airway diseases such as asthma COPD or bronchiectasis and the actual OB cases coming into light could just be the tip of the iceberg. Furthermore, Gothi et al.[30] elucidated that PH could be encountered in 19% of cases with OB and OB was as common as COPD in their study. In our study, 91 (27.7%) had ILD. It was the second most common cause of PH after OB. In patients with idiopathic pulmonary fibrosis, PH has been reported in 8%–80% of cases and the prevalence of PH increases with disease progression. The presence of PH markedly increases mortality in patients with ILD.[31] The PH in ILD is typical of mild-to-moderate degree, and progression is slow and occurs in tandem with disease progression. Our study had few limitations in the form of an inevitable referral bias and that measured PH noninvasively.
| Conclusion | | |
It is the first Indian study of its kind involving patients presenting with predominant respiratory symptoms, done on a large sample size of patients with an exhaustive analysis of multiple variables. Furthermore, it has brought into spotlight a very conspicuous fact that postinfectious OB is a crucial cause of PH in patients presenting to a pulmonologist and needs to be opportunely evaluated.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Rubin LJ. Primary pulmonary hypertension. N Engl J Med 1997;336:111-7.  |
| 2. | Barst RJ, Langleben D, Frost A, Horn EM, Oudiz R, Shapiro S, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004;169:441-7. |
| 3. | Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: A systematic review. Eur Respir J 2009;34:888-94. |
| 4. | Naeije R, Mélot C, Niset G, Delcroix M, Wagner PD. Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise. J Appl Physiol (1985) 1993;74:1666-71. |
| 5. | Chemla D, Castelain V, Provencher S, Humbert M, Simonneau G, Hervé P. Evaluation of various empirical formulas for estimating mean pulmonary artery pressure by using systolic pulmonary artery pressure in adults. Chest 2009;135:760-8. |
| 6. | Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC, Girgis RE, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 2009;179:615-21. |
| 7. | Naeije R, Torbicki A. More on the noninvasive diagnosis of pulmonary hypertension: Doppler echocardiography revisited. Eur Respir J 1995;8:1445-9. |
| 8. | Currie PJ, Seward JB, Chan KL, Fyfe DA, Hagler DJ, Mair DD, et al. Continuous wave Doppler determination of right ventricular pressure: A simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol 1985;6:750-6. |
| 9. | Chaouat A, Bugnet AS, Kadaoui N, Schott R, Enache I, Ducoloné A, et al. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005;172:189-94. |
| 10. | Torbicki A, Kurzyna M, Kuca P, Fijałkowska A, Sikora J, Florczyk M, et al. Detectable serum cardiac troponin T as a marker of poor prognosis among patients with chronic precapillary pulmonary hypertension. Circulation 2003;108:844-8. |
| 11. | ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-7. |
| 12. | Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Pulmonary arterial hypertension in France: Results from a national registry. Am J Respir Crit Care Med 2006;173:1023-30. |
| 13. | Tueller C, Stricker H, Soccal P, Tamm M, Aubert JD, Maggiorini M, et al. Epidemiology of pulmonary hypertension: New data from the Swiss registry. Swiss Med Wkly 2008;138:379-84. |
| 14. | Mehrotra R, Bansal M, Ksliwal RR, Trehan N. Epidemiology of pulmonary hypertension: Data from an Indian registry. J Clin Prev Cardiol 2012;2:51-7. |
| 15. | Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987;107:216-23. |
| 16. | Sleeper JC, Orgain ES, McIntosh HD. Primary pulmonary hypertension. Review of clinical features and pathologic physiology with a report of pulmonary hemodynamics derived from repeated catheterization. Circulation 1962;26:1358-69. |
| 17. | Algeo S, Morrison D, Ovitt T, Goldman S. Noninvasive detection of pulmonary hypertension. Clin Cardiol 1984;7:148-56. |
| 18. | Flowers NC, Horan LG. Subtle signs of right ventricular hypertrophy and their relative importance. Advances in electrocardiography. 1972;297. |
| 19. | Bossone E, Paciocco G, Iarussi D, Agretto A, Iacono A, Gillespie BW, et al. The prognostic role of the ECG in primary pulmonary hypertension. Chest 2002;121:513-8. |
| 20. | Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000;161:487-92. |
| 21. | Sims MW, Margolis DJ, Localio AR, Panettieri RA, Kawut SM, Christie JD. Impact of pulmonary artery pressure on exercise function in severe COPD. Chest 2009;136:412-9. |
| 22. | Paciocco G, Martinez FJ, Bossone E, Pielsticker E, Gillespie B, Rubenfire M. Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Eur Respir J 2001;17:647-52. |
| 23. | Nakamura A, Kasamatsu N, Hashizume I, Shirai T, Hanzawa S, Momiki S, et al. Effects of hemoglobin on pulmonary arterial pressure and pulmonary vascular resistance in patients with chronic emphysema. Respiration 2000;67:502-6. |
| 24. | Oswald-Mammosser M, Apprill M, Bachez P, Ehrhart M, Weitzenblum E. Pulmonary hemodynamics in chronic obstructive pulmonary disease of the emphysematous type. Respiration 1991;58:304-10. |
| 25. | Campbell EJ, Short DS. The cause of oedema in “corpulmonale”. Lancet 1960;1:1184-6. |
| 26. | Foshat M, Boroumand N. The evolving classification of pulmonary hypertension. Arch Pathol Lab Med 2017;141:696-703. |
| 27. | |
| 28. | Turton CW, Williams G, Green M. Cryptogenic obliterative bronchiolitis in adults. Thorax 1981;36:805-10. |
| 29. | Joshi JM, Gothi D. Post infectious obliterative bronchiolitis. Lung India 2006;23:75-7. [Full text] |
| 30. | Gothi D, Shah DV, Joshi JM. Clinical profile of diseases causing chronic airflow limitation in a tertiary care Centre in India. J Assoc Physicians India 2007;55:551-5. |
| 31. | Hamada K, Nagai S, Tanaka S, Handa T, Shigematsu M, Nagao T, et al. Significance of pulmonary arterial pressure and diffusion capacity of the lung as prognosticator in patients with idiopathic pulmonary fibrosis. Chest 2007;131:650-6. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
|
Search Pubmed for