sildenafil-citrate and Lung-Diseases--Interstitial

Patients with fibrotic interstitial lung disease have symptom control and quality of life (QoL) needs. This review aims to evaluate the evidence for the use of interventions in improving dyspnoea, other symptoms and QoL.. Eleven databases, relevant websites and key journals were hand-searched. Studies were assessed and data extracted independently by two researchers using standardised proformas. Meta-analyses were performed where possible with 95% CI.. 34 papers with 19 interventions in 3635 patients were included. Meta-analyses showed no significant effect of interferon γ-1b or sildenafil on 6-minute walking distance (6MWD) or dyspnoea. Pulmonary rehabilitation and pirfenidone had a positive effect on 6MWD (mean difference (95% CI) 27.4 (4.1 to 50.7)) and 24.0 (4.3 to 43.7), respectively), and pulmonary rehabilitation had a mixed effect on dyspnoea. Both pulmonary rehabilitation and sildenafil showed a trend towards significance in improving QoL. There was weak evidence for the improvement of 6MWD using oxygen; dyspnoea using prednisolone, diamorphine, D-pencillamine and colchicine; cough using interferon α and thalidomide; anxiety using diamorphine; fatigue using pulmonary rehabilitation; and QoL using thalidomide and doxycycline. A wide range of outcome scales was used and there were no studies with economic evaluation.. There is strong evidence for the use of pulmonary rehabilitation and pirfenidone to improve 6MWD and moderate evidence for the use of sildenafil and pulmonary rehabilitation to improve QoL. Future recommendations for research would include careful consideration of the dichotomy of radical and palliative treatments when deciding on how symptom and QoL outcome measures are used and data presented.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Cough; Dyspnea; Exercise Test; Fibrosis; Glucocorticoids; Heroin; Humans; Immunologic Factors; Lung; Lung Diseases, Interstitial; Narcotics; Oxygen Inhalation Therapy; Piperazines; Prednisolone; Purines; Pyridones; Quality of Life; Sildenafil Citrate; Sulfones; Thalidomide; Tubulin Modulators

Topics: Carbolines; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Phosphodiesterase 5 Inhibitors; Phosphoric Diester Hydrolases; Purines; Sildenafil Citrate; Tadalafil

About 10% of term neonates present with respiratory distress at birth. The most common aetiologies include transient tachypnoea of the newborn, pneumonia and meconium aspiration syndrome (MAS). Hyaline membrane disease (HMD) in a term infant occurs either as primary HMD, secondary surfactant deficiency or congenital surfactant dysfunction. A detailed history supported with appropriate radiological and laboratory investigations can help a clinician reach a diagnosis. We report a case of surfactant dysfunction disorder which presented as severe MAS and persistent pulmonary hypertension of the newborn. In the infant described, the significant history of a sibling death with severe neonatal respiratory disease led us to think of diffuse developmental lung diseases especially surfactant dysfunction syndromes. Exome sequencing detected a heterozygous missense variation in exon 21 of the ATP binding cassette protein member 3 (

Topics: ATP-Binding Cassette Transporters; Bronchodilator Agents; Diagnosis, Differential; Fatal Outcome; Humans; Infant, Newborn; Lung Diseases, Interstitial; Male; Meconium Aspiration Syndrome; Nitric Oxide; Persistent Fetal Circulation Syndrome; Pulmonary Surfactants; Respiration, Artificial; Sildenafil Citrate; Vasodilator Agents

A 12 year-old intact male Pembroke Welsh corgi weighing 10.8 kg was presented for evaluation of a 3-month history of dyspnea, and a 1-week history of exercise intolerance and anorexia. Severe hypoxemia (PaO

Topics: Animals; Blood Gas Analysis; Dog Diseases; Dogs; Fatal Outcome; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Sildenafil Citrate

In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process. PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology. CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs. Only one case of PH associated with CME has been reported worldwide.. A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea. The dog previously lived in the Cape Verdean islands. Physical examination showed signs of right-sided congestive heart failure and poor peripheral perfusion. Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing. Echocardiography showed severe pulmonary hypertension with an estimated pressure gradient of 136 mm Hg. On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia. A severe gamma hyperglobulinemia was also documented. Serology for Ehrlichia canis was highly positive. Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically. Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH.. This report illustrates that CME might be associated with significant pulmonary disease and should be considered as a possible differential diagnosis in dogs presenting with dyspnea and secondary pulmonary hypertension, especially in dogs that have been in endemic areas. This is important because CME is a treatable disease and its secondary lung and cardiac manifestations may be completely reversible.

Topics: Animals; Antiparasitic Agents; Dog Diseases; Dogs; Doxycycline; Ehrlichiosis; Heart Failure; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Pyridazines; Radiography, Thoracic; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

Interstitial lung diseases (ILD) are often associated with pulmonary hypertension (PH). This study aimed to evaluate the therapeutic benefit of phosphodiesterase-5 (PDE-5) inhibitors in pulmonary hypertension secondary to ILD.. Patients with ILD and PH were treated with sildenafil or tadalafil. Right heart catheterization was performed before and after a minimum of 3-month treatment. In addition, lung function, 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration were assessed.. Ten ILD patients (three female, mean age 64.4 ± 9.0 years, six with idiopathic pulmonary fibrosis (IPF), four with hypersensitivity pneumonitis, (HP)) with significant precapillary PH (mean pulmonary artery pressure (PAPm) ≥ 25 mmHg, pulmonary vascular resistance (PVR) > 280 dyn*s*cm(-5) ; pulmonary artery wedge pressure (PAWPm) ≤ 15 mmHg) were treated with either sildenafil (n = 5) or tadalafil (n = 5). Pulmonary haemodynamics were severely impaired at baseline (PAPm 42.9 ± 5.4 mmHg; cardiac index (CI) 2.7 ± 0.6 L/min/m2; PVR 519 ± 131 dyn × sec × cm(-5)). After mean follow-up of 6.9 ± 5.8 months an increase in CI (2.9 ± 0.7 L/min/m2 , P = 0.04) and a decrease in PVR (403 ± 190 dyn × sec × cm(-5) , P = 0.03) were observed. 6MWD and BNP did not change significantly.. Our data suggest that treatment with PDE-5 inhibitors improves pulmonary haemodynamic patients with PH secondary to ILD.

Topics: Aged; Aged, 80 and over; Carbolines; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Pilot Projects; Piperazines; Purines; Respiratory Function Tests; Sildenafil Citrate; Sulfonamides; Tadalafil; Walking

Therapy with sildenafil has been shown to decrease pulmonary vascular resistance and may improve functional status in patients with interstitial pneumonia (IP) and pulmonary hypertension (PH). Patients with IP and PH defined by a mean pulmonary artery pressure (MPAP) of > or = 25mm Hg on right-heart catheterization were followed up in an open-label study of sildenafil. A multilateral evaluation was conducted before, and after 3 months of therapy. We studied 11 patients [8 men and 3 women, mean age 66.5] 6 of whom had IPF (1 with usual interstitial pneumonia {UIP}), 2 with IIP, and 3 with collagen-vascular disease interstitial pneumonia (CVD-IP). The mean modified Medical Research Council (MRC) score was 3.0 +/- 0.89, baseline dyspnea index (BDI) score was 4.5 +/- 1.9, % VC was 58.7 +/- 15.6%, percentage of carbon monoxide diffusing capacity (%DLco) was 20.0 +/- 10.9%, six-minute walk distance (6MWD) was 269.8 +/- 105.5m, shuttle walking test (SWT) was 179.1 +/- 99.7m, St. George Respiratory Questionnaire (SGRQ) was 70.9 +/- 15.6, mean pulmonary artery pressure (MPAP) was 33.8 +/- 7.61mm Hg, and pulmonary vascular resistance index (PVRI) was 658.9 +/- 236.1 dynes x s x cm(-5) x m2. After 3 months of therapy, improvements in BDI (< or = -1), 6MWD (> or = 20%), SWT (> or = 20%), and SGRQ (< or = -7) were observed in 4, 2, 3, and 6 patients, respectively. Improvements in MPAP (< or = - 20%) and PVRI (< or = -20%) were observed in 2 and 3 patients, respectively. No parameter showed statistically significant differences. We conclude that sildenafil may improve dyspnea, exercise tolerance and health-related quality of life (QOL) in some IP patients with PH.

Topics: Aged; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Limited data suggest a benefit following sildenafil treatment in patients with pulmonary hypertension (PH) and interstitial lung disease (ILD). The role of sildenafil in the management of PH in ILD is not clear. We report our experience of ILD patients with PH after 6-month sildenafil therapy.. We reviewed 15 patients (mean age 55 ± 15 years; 8 men) with ILD (mean FVC 52.6 ± 15.4%) and PH (mean right ventricular systolic pressure 73.8 ± 17.8 mm Hg). Median brain natriuretic peptide: 37 (5-452) pmol/L; mean 6MWD: 156 ± 101 m.. Following 6-month treatment with sildenafil, brain natriuretic peptide levels were lower (n = 12, P = 0.03), 6MWD was higher (n = 6, P < 0.05), but no change in right ventricular systolic pressure (n = 11) was demonstrated.. Our observations suggest that sildenafil may be useful in the management of PH in ILD. Controlled trials are warranted before therapeutic recommendations can be made.

Topics: Cohort Studies; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents; Walking

A 54-year-old woman with a 20-year history of Raynaud phenomenon was admitted to our hospital complaining of progressive dyspnea on exertion since 5 years previously. Interstitial lung disease was diagnosed, accompanied by pulmonary arterial hypertension (PAH) associated with systemic sclerosis. After oxygen therapy and treatment with sildenafil, her clinical condition and PAH gradually improved. However, she was readmitted due to deterioration of Raynaud phenomenon and progressive dyspnea in March 2009. Right heart catheterization findings demonstrated that her mean pulmonary arterial pressure (PAP) was elevated, at 48 mmHg. Bosentan was therefore added to an increased dose of sildenafil. Consequently, her dyspnea, 6-min walking distance, serum brain natriuretic peptide level, and PAP improved. Combination therapy with bosentan and sildenafil was effective for this case of refractory PAH associated with fibrotic lung in systemic sclerosis.

Topics: Antihypertensive Agents; Bosentan; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Middle Aged; Piperazines; Purines; Scleroderma, Systemic; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Pulmonary hypertension (PH) is an important cause of mortality in systemic sclerosis (SSc), where it can be isolated (pulmonary arterial hypertension [PAH]) or associated with interstitial lung disease (ILD). This study was undertaken to characterize determinants of survival among SSc patients with either type of PH who received PAH-specific therapy.. Consecutive SSc patients with PAH or ILD-associated PH confirmed by right heart catheterization were included in the study. Kaplan-Meier and Cox proportional hazards models were used to compare survival between SSc patients with PAH and those with ILD-associated PH and to identify predictors of survival.. Fifty-nine patients (39 with PAH and 20 with ILD-associated PH) were identified. The majority (15 of 20 with ILD-associated PH and 27 of 39 with PAH) received an endothelin receptor antagonist as initial therapy. Median followup time was 4.4 years (range 2.7-7.4 years). Survival was significantly worse in SSc patients with ILD-associated PH than in those with PAH (1-, 2-, and 3-year survival rates 82%, 46%, and 39% versus 87%, 79%, and 64%, respectively; P < 0.01 by log rank test). In a multivariable analysis, ILD-associated PH was associated with a 5-fold increase in risk of death compared with PAH. Pulmonary vascular resistance index was also an independent predictor of mortality in the overall cohort (hazard ratio 1.05, P < 0.01) and was a significant univariable risk factor in each group separately. Type of initial PAH therapy and the use of warfarin were not related to survival.. Survival in SSc complicated by PH remains poor despite currently available treatment options. While therapy may be associated with improved survival in PAH compared with historical controls, the prognosis for patients with ILD-associated PH is particularly grim. Early diagnosis and treatment may improve outcomes since worsening hemodynamic factors were associated with reduced survival.

Topics: Bosentan; Cohort Studies; Comorbidity; Endothelin Receptor Antagonists; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Isoxazoles; Lung Diseases, Interstitial; Male; Maryland; Middle Aged; Piperazines; Prognosis; Proportional Hazards Models; Purines; Receptors, Endothelin; Scleroderma, Diffuse; Scleroderma, Systemic; Sildenafil Citrate; Sulfonamides; Sulfones; Survival Rate; Thiophenes; Vasodilator Agents

The present authors report the case of an adult with chronic granulomatous disease who developed an unusual lung fibrosis associated with severe pulmonary hypertension. Histological analysis of a lung biopsy showed a diffuse infiltration with pigmented macrophages without granulomas, which particularly involved the pulmonary arterial and venular walls. Clinical and histological findings were suggestive of pulmonary veno-occlusive disease. Such a clinical association has not been previously described in the literature and might be due to the persistent expression of gp91phox at a very low level. In conclusion, the present case report illustrates a novel manifestation of chronic granulomatous disease.

Topics: Adult; Biopsy; Bronchoalveolar Lavage; Bronchoscopy; Diagnosis, Differential; Diuretics; Furosemide; Granulomatous Disease, Chronic; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Respiratory Function Tests; Sildenafil Citrate; Smoking; Sulfones; Tomography, X-Ray Computed

The endothelin system plays an important role in the development of pulmonary hypertension. Several studies have suggested that interfering with the function of the endothelin system will be helpful in pulmonary hypertension treatment. In the present study, we investigated the preventive and therapeutic effects of sildenafil on pulmonary hypertension in monocrotaline-treated rats. In the preventive study, the level of mean pulmonary arterial pressure, right ventricular divide, left ventricular and septum, small pulmonary arterial morphologic and elastic fiber changes were highly improved in the treated group (P<0.05). The expressions of endothelin-1 A type receptors on small pulmonary arterial hypertension were significantly reduced in the sildenafil-treated group (P<0.05). The ET-1 level in plasma was increased in the sildenafil-treated group, but did not reach significance. Emphysema, interstitial pneumonia were significantly improved in the sildenafil-treated group. The same findings were also observed in the therapeutic study. The present results suggest that sildenafil can prevent and reverse the development of pulmonary hypertension in monocrotaline-treated rats by improving the function of endothelin system in pulmonary arteries.

Topics: Administration, Oral; Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Endothelin-1; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Lung Diseases, Interstitial; Male; Monocrotaline; Piperazines; Pulmonary Artery; Pulmonary Emphysema; Purines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Sildenafil Citrate; Sulfones; Time Factors; Vasodilator Agents