Pleuropulmonary Fibrosis Research Articles

Evolución clínica, funcional y radiológica de pacientes trasplantados pulmonares con síndrome de bronquiolitis obliterante y disfunción de injerto pulmonar restrictivo

The main long-term complication in lung transplant patients is chronic graft dysfunction identified as bronchiolitis obliterans, and there is a new pattern called Restrictive Graft Dysfunction. Objective: To evaluate spirometric, radiological and clinical follow-up among patients with bronchiolitis obliterans syndrome (BOS) and Restrictive Allograft Syndrome (RAS) after lung transplantation. Methodology: Lung transplant recipients ’ clinical records were reviewed from 1999 to 2017. We carried out a follow up of spirometry, chest tomography imaging and associated factors: cytomegalovirus (CMV) infection, gastroesophageal reflux (GER) and episodes of acute rejection. Survival was analyzed by Kaplan Meier. Results: Out of 88 lung transplant patients, 40 developed chronic graft dysfunction: 31 (80%) presented BOS and 9 (20%) had RAS. Mean age: 47 yr.o. in BOS and 46 yr. o. in RAS. Lung fibrosis was the primary pathology predominant in both conditions. In BOS were reported 14 episodes of acute rejection (50%), CMV infection in 18% and active GER in 26%. In RAS there were 5 episodes of acute rejection (62%), CMV infection in 13% and active GER in 67% (p = 0.02). VEF1 follow-up at 1-2-4-5 years averaged 67, 65, 60 and 8% of reference value in BOS and 61, 65, 62 and 45% in RAS respectively. CT scans showed hyperinflation in BOS and upper pleuropulmonary fibrosis in RAS. BOS survival time was 96.9 months versus 65.6 months in RAS (p = 0.06). Conclusiones: Restrictive dysfunction presented a lower survival rate than BOS. GER was associated with restrictive rejection. Chest tomography differs in both types of chronic rejection.

Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis.

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A.fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A.fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.

Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma.

Cabergoline is related to an elevated risk of fibrotic adverse reactions including cardiac valvular and pleuropulmonary fibrosis. We investigated pulmonary and cardiac valve fibrosis and immunological markers before and after 3 and 12 months of treatment with cabergoline in women with prolactinoma. The study included thirty-two women with newly diagnosed prolactinoma and 28 healthy women. CAB cumulative dose was 7.8±5.5 mg after 3-month therapy, and 31±22 mg after 12-month follow-up. The risk of autoimmune adverse fibrotic reactions related to CAB treatment including cardiac valvulopathy and pulmonary fibrosis were assessed by a transthoracic echocardiography and pulmonary function tests, respectively. Immunological markers including Antistreptolysin O, Rheumatoid factor, Immunglobuline E, Antinuchlear antibody were also evaluated. Before the start of CAB therapy, the total prevalence of trace grade of mitral, aortic, pulmonic, and tricuspid valve regurgitations were found as 34%, 3%, 6.3%, and 39 % respectively in women with prolactinoma. After improving of prolactin levels with CAB treatment, no change was found in the prevalence of the all valve regurgitations. There was no deterioration in pulmonary function tests. Rheumatoid factor was found higher in newly diagnosed women with prolactinoma than in healthy women (p=0.01), and this was improved by CAB therapy (p=0.005). The prospective study indicated that sufficient cabergoline doses for a period of one year treatment of prolactinoma were not found to be related to fibrotic adverse reactions including cardiac valvular and pulmonary fibrosis or increased levels of immunological marker, apart from rheumatoid factor. For the first time Rf was found higher in newly diagnosed women with prolactinoma and was improved after cabergoline therapy.

Lung and pleural fibrosis in asbestos-exposed workers: a risk factor for pneumonia mortality

Lungs exposed to occupational dust may be especially vulnerable to fatal infections. We followed up asbestos-exposed workers (n=590) originally screened for lung cancer with computed tomography and scored for pleuropulmonary fibrosis. We checked these workers' influenza and pneumonia mortality data (ICD-10 codes J10-J18) in the national register. In total, 191 deaths, including 43 deaths from infectious pneumonia, occurred in 6158 person-years of follow-up (mean follow-up time 10·44 years). 'Some interstitial fibrosis' [hazard ratio (HR) 2·26, 95% confidence interval (CI) 0·98-5·19, P=0·06] and 'definite interstitial fibrosis' (HR 3·70, 95% CI 1·22-11·23, P=0·02) were associated with an increased risk of death from pneumonia compared to no fibrosis. Asbestosis patients, i.e. those with both asbestos exposure and lung fibrosis, therefore appear to be particularly at risk for death from pneumonia. These patients should be vaccinated against influenza and Pneumococcus.

Histopathology of Aspiration Pneumonia Not Associated With Food or Other Particulate Matter

Aspiration pneumonia most often presents in surgical lung biopsies as a granulomatous pneumonia with acute inflammation, microabscesses, and a granulomatous reaction to food or other particulate matter. In this study of 10 patients with clinical aspiration in whom surgical lung biopsy was performed, 3 additional patterns of lung injury were seen: organizing pneumonia (4 patients); acute diffuse alveolar damage (3 patients); and chronic bronchiolitis (3 patients), in whom 2 had evidence of extensive pleuropulmonary fibrosis and scarring. This study adds to the earlier described literature on granulomatous reactions to food and particulate matter in the lung by alerting pathologists to other histopathologic manifestations of aspiration-induced lung injury in surgical lung biopsies.

Inflammatory aneurysm of the abdominal aorta in a patient treated with ropinirole

Retroperitoneal fibrosis, inflammatory aneurysm of the abdominal aorta and perianeurysmal retroperitoneal fibrosis are three closely related entities that belong to the spectrum of chronic periaortitis [1]. Retroperitoneal and pleuropulmonary fibrosis are well known but rare complications of the treatment with ergolinic dopamine agonists of Parkinson’s disease [2, 3]. To our knowledge, ropinirole, a non-ergot derived dopamine agonist, has never been associated with fibrotic complications localized to the retroperitoneal space. A 72-year-old man was admitted to our clinic because of a febrile illness with significant anorexia and fatigue. At presentation, he suffered from moderately advanced Parkinson’s disease, which was diagnosed 11 years ago. His treatment consisted of levodopa/carbidopa and ropinirole throughout his disease course. At the time of admission he was on 1.35 g/day of levodopa and 15 mg/day of ropinirole. On admission, apart from a fever of 38.5 C and the parkinsonian signs, his physical examination was unremarkable. Routine laboratory tests showed moderate normochromic-normocytic anemia (hemoglobin 8.9 g%), elevation of C-reactive protein level (14 mg%), elevated erythrocyte sedimentation rate (124 mm/ h), ferritin (1381 ng/ml) and fibrinogen (7.9 g/l). Further investigation revealed mild increase of serum IgA (510 mg/dl), beta2 microglobulin (4.03 mg/l) and total globulin level (3.7 g/dl). Extensive serological studies for autoimmune and infectious disorders were either normal or negative, whereas bone marrow aspirate and biopsy findings were compatible with reactive changes secondary to chronic inflammation. Both chest X-ray and chest CT scans showed no abnormalities. CT imaging of the abdomen revealed findings indicative of periaortic edema and inflammatory soft tissue formation without aneurysm (Fig. 1). Ropinirole withdrawal was suggested, but the patient declined. Administration of i.v. methylprednisolone at 80 mg/day resulted in complete relief of symptoms within a few days, and acute phase reactants started to decline. Similarly, anemia gradually responded to steroid therapy. The patient remained in clinical remission during steroid tapering to a maintenance dose of 10 mg/day. However, a follow-up CT examination performed 3 months later demonstrated a 4 cm saccular aneurysm arising from the right anterolateral portion of the aorta (Fig. 2). In this report we present a patient who developed inflammatory aneurysm of the abdominal aorta while on long-term treatment with ropinirole. In this disorder fibroinflammatory tissue develops around a dilated aorta, but does not cause obstructions of the adjacent structures. Inflammatory aneurysm of the abdominal aorta together with retroperitoneal fibrosis and perianeurysmal retroperitoneal fibrosis are believed to have a common autoimmune pathogenesis and share many clinical, laboratory and histological features [4]. D. Parissis (&) B’ Department of Neurology, Aristotle University of Thessaloniki, AHEPA Hospital, 1, Stilponos Kyriakidi Str, 546 36 Thessaloniki, Greece e-mail: dparissis@gmail.com

Absence of major fibrotic adverse events in hyperprolactinemic patients treated with cabergoline

Cabergoline, a dopamine agonist used to treat hyperprolactinemia, is associated with an increased risk of fibrotic adverse reactions, e.g. cardiac valvular fibrosis, pleuropulmonary, and retroperitoneal fibrosis. This study evaluated the prevalence and risk of fibrotic adverse reactions during cabergoline therapy in hyperprolactinemic and acromegalic patients. A cross-sectional study was conducted in a University Hospital. A total of 119 patients with hyperprolactinemia and acromegaly who were on cabergoline therapy participated in the study. All patients were requested to undergo a cardiac assessment, pulmonary function test, chest X-ray, and blood tests as recommended by the European Medicine Agency. Matched controls were recruited to compare the prevalence of valvular regurgitation. Cardiac valvular fibrosis was evaluated by assessing valvular regurgitation and the mitral valve tenting area (MVTa). The risk of pleuropulmonary fibrosis was assessed by a pulmonary function test, a chest X-ray, and if indicated, by additional imaging studies. The prevalence of clinically relevant valvular regurgitation was not significantly different between cases (11.3%) and controls (6.1%; P=0.16). The mean MVTa was 1.27+/-0.17 and 1.24+/-0.21 cm(2) respectively (P=0.54). Both valvular regurgitation and the MVTa were not related to the cumulative dose of cabergoline. A significantly decreased pulmonary function required additional imaging in seven patients. In one patient, possible early interstitial fibrotic changes were seen. Lung function impairment was not related to the cumulative cabergoline dose. Cabergoline, typically dosed for the long-term treatment of hyperprolactinemia or acromegaly, appears not to be associated with an increased risk of fibrotic adverse events.

Rounded atelectasis and respiratory compromise secondary to pergolide use

Rounded atelectasis is an unusual form of peripheral atelectasis that develops as a consequence of pleural disease. It is usually thought to be a benign process after malignancy and infection have been excluded. Pergolide is an ergot-derived dopamine agonist that has been associated with pleuropulmonary fibrosis and fibrotic cardiac valve disease. Pergolide-associated rounded atelectasis has occurred in patients with known asbestos exposure. We report a patient with no known asbestos exposure who developed rounded atelectasis and subsequent symptomatic diffuse restrictive pleural disease. Physicians should consider drugs early on in their work-up of rounded atelectasis as discontinuation of the agent may reverse the process.

Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson's disease

Retroperitoneal and pleuropulmonary fibrosis are well known but rare complications of the treatment of Parkinson's disease with ergolinic dopamine agonists; however, until now, these complications have not substantially affected the routine clinical use of these drugs. The occurrence of restrictive valvular heart disease during treatment with pergolide and cabergoline caused concern about the safety of dopamine agonists in Parkinson's disease. Specifically, there is uncertainty whether fibrotic cardiac valvulopathy is due to exposure to these two ergolinic dopamine agonists or whether the abnormality is reversible. Changes in the heart valves can incur additional disability and worsen the clinical disorders of Parkinson's disease. Population studies of patients with Parkinson's disease compared with non-parkinsonian controls have reported that pergolide and cabergoline have a similar risk of inducing fibrotic changes in cardiac valve leaflets. The fibrotic changes cause thickening, retraction, and stiffening of valves, which result in incomplete leaflet coaptation and clinically significant regurgitation, and have necessitated surgical valve replacement in some patients. Pergolide and cabergoline have high affinity for the 5-HT(2B) serotonin receptors, which are expressed in heart valves and might mediate mitogenesis and, in turn, the proliferation of fibroblasts. When analysed together, current population studies of similar designs and doses report 102 patients on cabergoline, 245 patients on pergolide, 181 patients on non-ergot agonists (pramipexole and ropinirole), and 177 non-parkinsonian controls. The frequency of moderate-to-severe regurgitation in at least one heart valve was higher in patients receiving cabergoline or pergolide than in patients taking non-ergot agonists or controls, and the incidence of new-onset valvulopathy was high in patients taking the ergot-derived drugs. WHERE NEXT?: Because of the routine prescription of pergolide and cabergoline, the switching of patients to different treatment regimens might be difficult. Moreover, whether the fibrotic changes are reversible is unknown. Finally, these adverse events do not occur in all patients, and no susceptibility factors are known. Prospective studies will assess the full effect of these abnormalities and help establish whether and when mitral valve tenting area abnormalities become clinically relevant during chronic treatment. The exact pathway leading to valvulopathy is unknown, although agonism of 5-HT(2B) receptors in the heart is implicated as a mediator in the process. Other ergolinic dopamine agonists, such as lisuride, and non-ergot dopamine agonists are devoid of 5-HT(2B) agonistic activity; therefore, their use might not induce fibrotic changes in heart valves. However, further prospective studies are needed. Such studies should also clarify the clinical relevance of mild-to-moderate echocardiographic changes and their natural history. Because of the clinical consequences of the adverse reactions, we suggest that affinity for 5-HT(2B) receptors is routinely tested in future drugs, in the laboratory or in animals, before they are given to patients.

The treatment of restless legs syndrome

The objective was to provide an overview of the options for treatment of primary restless legs syndrome (RLS), by analysing the relevant clinical trials for RLS. The patients considered were those affected with primary (or idiopathic) RLS. Levodopa, pramipexole, ropinirole, transdermal rotigotine, pergolide and cabergoline all show clear evidence for efficacy in short-term treatment. Adverse events with these drugs are those usual for dopaminergic agents, and are usually mild and reversible, probably because of the relatively low doses needed. Augmentation, i.e., worsening of RLS symptoms not due to progression of the disease, however, represents a worrisome side effect of dopaminergic drugs, especially levodopa. Ergot-derived dopaminergic agents should also be periodically checked for the possible development of multivalvular heart disease and pleuropulmonary fibrosis. Gabapentin is another drug also having clear evidence for efficacy. In conclusion, dopaminergic agents represent the first line of treatment for idiopathic RLS.

Methysergide-Induced Valvular Heart Disease: A Report of 2 Cases

Methysergide is a serotonin antagonist and is used as a long-term prophylactic treatment for migraine. Although many patients experience adequate control of migraine episodes, methysergide has been reported to cause retroperitoneal and pleuropulmonary fibrosis. Cardiovascular side effects mainly in the form of valvular fibrosis have been less recognized. We report 2 cases of methysergide-related mitral valve fibrosis.

Pleuropulmonary Fibrosis After Long-term Treatment With the Dopamine Agonist Pergolide for Parkinson Disease

Dopamine agonists are increasingly used in the treatment of Parkinson disease, but they may cause serious adverse effects. In December 1983, symptoms of Parkinson disease developed in a 55-year-old man with no history of pulmonary disease, smoking, or asbestos exposure. He began treatment with dopamine agonists bromocriptine mesylate (in 1984) and pergolide mesylate (in 1989). In late 2000, pulmonary symptoms developed. Chest radiographs and computed tomographic findings showed a mass in the right upper lobe and effusion. A biopsy specimen showed pleural and parenchymal fibrosis. This syndrome resolved after cessation of pergolide therapy and a switch to pramipexole dihydrochloride. This case draws attention to the association of long-term ergot dopamine agonist therapy with pleuropulmonary fibrosis, which can develop as late as 11 years after the initiation of therapy. We also review evidence that the risk of this complication is substantially lower with the newer nonergot dopamine agonists.

Respiratory Complications of Parkinson's Disease

Patients with Parkinson's disease are at risk for pulmonary complications as a consequence of both the underlying disease pathology and the side effects of medication. Degeneration of the substantia nigra and subsequent loss of dopaminergic neurons may produce changes in ventilatory parameters. Upper airway obstruction and chest wall restriction are both common, and both may respond to levodopa. However, therapy for Parkinson's may also contribute to pulmonary morbidity. Overtreatment with levodopa causes respiratory dyskinesia that may be difficult to differentiate from complications of the disease itself. Therapy with ergot derivatives may cause pleuropulmonary fibrosis. Pneumonia resulting from the respiratory complications remains a significant cause of morbidity and mortality in Parkinson's disease.

Pleuropulmonary Disease Due to Pergolide Use for Restless Legs Syndrome

Pergolide is an ergot-derived dopamine agonist used in Parkinson's disease and, increasingly, in restless legs syndrome. We report a patient with a 2.5-year history of weight loss, pleuropulmonary fibrosis, and exudative pleural effusion that developed insidiously while taking this medication. The extensive and invasive workup that preceded the diagnosis highlights the difficulty in attributing such a process to a drug reaction. This is the second report of such a reaction to pergolide, which is one of the increasing number of ergot-derived compounds in common clinical use.

Low dose bromocriptine‐induced pleural effusion and pleuropulmonary fibrosis

We describe a parkinsonian patient who developed a slight asymptomatic pleural effusion during prolonged therapy with low dose bromocriptine (BCR) in addition to levodopa, following prior treatment with CQA 206-291. A moderate increase of BCR dosage prompted a severe pleuropulmonary inflammatory reaction with polyclonal activation and elevated serum liver enzymes, which normalized following withdrawal of the drug. The clinical syndrome and close relation to BCR treatment are in keeping with a diagnosis of BCR-related pleuropulmonary fibrosis (PPF). Features of this case are compared with previous reports on dopamine (DA) agonist-related PPF. This case supports earlier suggestions of polyclonal activation in DA agonist-related PPF and suggests hepatic involvement and dose dependency.

Endocardial Fibrosis Associated with Methysergide Therapy.

Meeting Abstracts1 May 1973Endocardial Fibrosis Associated with Methysergide Therapy.Dhirendra S. Bana, M.D., Perry S. MacNeal, M.D., F.A.C.P., Philip M. LeCompte, M.D., Yogendra Shah, M.D., John R. Graham, M.D.Dhirendra S. Bana, M.D.Search for more papers by this author, Perry S. MacNeal, M.D., F.A.C.P.Search for more papers by this author, Philip M. LeCompte, M.D.Search for more papers by this author, Yogendra Shah, M.D.Search for more papers by this author, John R. Graham, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-821_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMethysergide is probably causally related to the development of cardiac lesions in some patients taking this drug for headaches. We report our observations of the development and progress of cardiac murmurs in 36 of our own patients and 12 patients of other physicians, all taking methysergide. Murmurs were predominantly of aortic and mitral valve origin. Twelve patients had complete and 15 patients partial regression of the murmurs, 6 to 70 months after stopping use of the drug. Nine patients had retroperitoneal fibrosis, and two patients had pleuropulmonary fibrosis in addition to endocardial lesions. In four patients pathological material was available... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts, and Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDrug Action, Reaction, and Interaction 1 May 1973Volume 78, Issue 5Page: 821-822KeywordsDrugsFibrosisLesions Issue Published: 1 May 1973 PDF DownloadLoading ...