Misbah Baqir

Amyloid-associated cystic lung disease in primary Sjögren's syndrome

BACKGROUND Cystic lung disease can be seen in patients with Sjögrens syndrome (SS) and is generally thought to be due to lymphocytic interstitial pneumonia. METHODS Using computer-assisted search we identified patients with primary SS seen at Mayo Clinic, Rochester, MN during a 14-year period from 1997 to 2010 who were diagnosed with pulmonary amyloidosis confirmed on lung biopsy. Clinical records, imaging studies, and pathologic specimens were reviewed to delineate presenting features, diagnostic evaluation, and clinical course. RESULTS Eight patients (7 women, 1 man) with primary SS were diagnosed with pulmonary amyloidosis by lung biopsy (7 surgical, 1 bronchoscopic). Their median age was 55 years (range, 32-75 years) and all were nonsmokers. Presenting symptoms included dyspnea and cough but 4 patients presented with radiologic abnormalities in the absence of respiratory symptoms. CT findings included cystic lesions and nodular opacities in all eight patients. PET scan performed in six patients did not reveal (18)F-2-deoxyglucose (FDG) uptake except in one nodule with borderline uptake. Lung biopsy demonstrated the presence of amyloid in all patients and was associated with mucosa-associated lymphoid tissue (MALT) lymphoma in three patients. Pulmonary function results were normal in five patients and revealed mild impairment in a mixed pattern in one patient. CONCLUSIONS We conclude cystic and nodular lung lesions seen in patients with primary SS can represent amyloidosis which can be associated with MALT lymphoma in some of these patients.

Predictors of diagnosis and survival in idiopathic pulmonary fibrosis and connective tissue disease-related usual interstitial pneumonia.

BackgroundAlthough usual interstitial pneumonia (UIP) appears to portend better survival when associated with connective tissue disease (CTD-UIP), little is known about the presenting clinical, radiologic, and pathologic features that differentiate pathologically confirmed UIP with CTD from idiopathic pulmonary fibrosis (IPF). In patients with atypical radiologic and clinical features, what specific findings predict underlying IPF vs. CTD-UIP diagnosis and their respective long term survival?MethodsA large retrospective cohort analysis was done of consecutive patients seen from 1995 through 2010 with biopsy confirmed UIP completed or reviewed at our institution. CTD-UIP was defined by independent rheumatology consultation with exclusion of all other secondary causes of lung fibrosis. Primary clinical data was collected and compared for IPF and CTD-UIP along with logistic regression performed for predictors of disease likelihood and Cox proportional hazards analysis for predictors of survival.ResultsSix hundred and twenty five patients were included in the study of which 89 had diagnosed CTD-UIP representing 7 disease entities. Survival was better among those with CTD-UIP except in UIP associated with rheumatoid arthritis, which had similar presenting features and survival to IPF. Predictors of underlying CTD included female gender, younger age, positive autoimmune serology, and inconsistent presenting radiologic findings. Only age and forced vital capacity corrected for a priori covariates were predictive of survival in CTD-UIP.ConclusionsUIP pathology occurs frequently among patients with atypically presenting clinical and radiologic features, and may represent IPF or CTD-UIP with improved prognosis if underlying CTD is diagnosed. Presenting radiologic and pathologic features alone are not predictive of underlying secondary cause or survival between the two groups.

Air travel and pneumothorax

The number of medical emergencies onboard aircraft is increasing as commercial air traffic increases and the general population ages, becomes more mobile, and includes individuals with serious medical conditions. Travelers with respiratory diseases are at particular risk for in-flight events because exposure to lower atmospheric pressure in a pressurized cabin at cruising altitude may result in not only hypoxemia but also pneumothorax due to gas expansion within enclosed pulmonary parenchymal spaces based on Boyles law. Risks of pneumothorax during air travel pertain particularly to those patients with cystic lung diseases, recent pneumothorax or thoracic surgery, and chronic pneumothorax. Currently available guidelines are admittedly based on sparse data and include recommendations to delay air travel for 1 to 3 weeks after thoracic surgery or resolution of the pneumothorax. One of these guidelines declares existing pneumothorax to be an absolute contraindication to air travel although there are reports of uneventful air travel for those with chronic stable pneumothorax. In this article, we review the available data regarding pneumothorax and air travel that consist mostly of case reports and retrospective surveys. There is clearly a need for additional data that will inform decisions regarding air travel for patients at risk for pneumothorax, including those with recent thoracic surgery and transthoracic needle biopsy.

Utility of bronchoscopy in pulmonary Langerhans cell histiocytosis.

Background:Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon form of interstitial lung disease and is usually smoking-related when seen in adults. There are relatively little data regarding the utility of bronchoscopic lung biopsy for this disorder. Methods:A computer-assisted search was carried out to identify patients with PLCH seen at Mayo Clinic Rochester, MN from 1997 to 2012 and who underwent bronchoscopy with lung biopsy. Approval was obtained from the Mayo Foundation Institutional Review Board before beginning the study. Medical records of these patients were reviewed to extract data with regard to demographic and clinical features, imaging studies, and biopsy results. Results:Thirty-eight patients with PLCH underwent diagnostic bronchoscopy with biopsies. Their median age was 39.5 years (range, 21 to 66 y) and included 24 women. Thirty-two patients (84%) were current smokers at the time of the diagnosis, 5 were ex-smokers (13%), and 1 was a never-smoker (3%). The diagnosis of PLCH required the presence of typical histopathologic features on surgical or bronchoscopic lung biopsy, >5% CD1a-positive cells in the bronchoalveolar lavage (BAL), and/or biopsy of an extrapulmonary site in the presence of clinical and chest computed tomographic findings compatible with the diagnosis. Bronchoscopic biopsy yielded diagnostic specimens that allowed the diagnosis of PLCH in 19 patients (50%). CD1a immunostaining of BAL cells had been performed in 8 patients and demonstrated ≥5% CD1a-positive BAL cells in 3 additional patients (8%). Conclusions:We conclude that bronchoscopic lung biopsy is useful in the diagnosis of PLCH and should be the initial method of obtaining diagnostic specimens.

18F-FDG PET Scanning in Pulmonary Amyloidosis

18F-FDG PET plays an important role in the evaluation of patients with lung malignancies but can lead to false-positive and false-negative results. Very little is known about 18F-FDG PET scanning in amyloidosis. Methods: A computer-assisted search of medical records was conducted to identify subjects with pulmonary amyloidosis (confirmed by biopsy) who were seen at the Mayo Clinic during a 15-y period between January 1, 1997, and December 31, 2011, and had a PET scan available for current review. Results: Eighteen patients were diagnosed to have amyloidosis by lung biopsy (15 surgical, 2 transthoracic needle, and 1 bronchoscopic). The mean age of the patients was 64.8 y (range, 32–80 y). Seventeen patients had primary amyloidosis, including 5 with Sjögren syndrome, 1 with rheumatoid arthritis, and 1 with multiple myeloma. The most common abnormal findings on the chest CT scan were pulmonary nodules (n = 14), followed by cysts (n = 6) and reticular opacities (n = 4). Eight patients had positive 18F-FDG PET results (intrathoracic 18F-FDG uptake), including 4 patients with coexisting mucosa-associated lymphoid tissue lymphoma (maximal standardized uptake value [SUVmax] range, 3.1–6.7) and 1 patient with a pleural plasmacytoma (SUVmax, 7.2); the remaining 3 patients had amyloid only (SUVmax range, 2.1–3.2). Ten patients with negative PET results included 3 additional patients with mucosa-associated lymphoid tissue lymphoma. Conclusion: Positive 18F-FDG PET results, especially with an SUVmax of more than 3, in patients with pulmonary amyloidosis should raise suspicion about associated lymphoma or plasmacytoma, but negative PET results do not exclude the presence of such neoplasms.

Emphysematous changes in hypersensitivity pneumonitis: A retrospective analysis of 12 patients

Introduction Emphysema is most commonly associated with smoking but also occurs in hypersensitivity pneumonitis (HP). The aim of this study was to further explore this relationship. Methods A retrospective, computer-assisted search was performed to identify patients with HP seen at Mayo Clinic in Rochester, Minnesota, from January 1997 through February 2014. Demographic, clinical, and imaging features were analyzed. Patients were excluded if they had a smoking history of 10 pack-years or more. Results Twelve patients (9 males) with HP and computed tomographic evidence of emphysema were identified. Ten were never smokers and 2 were ex-smokers. The median age at diagnosis was 47 (range, 29–77) years; median symptom duration was 2.2 (range, 0.2–13.4) years. The most common presenting symptoms were dyspnea (83%) and cough (67%). On pulmonary function testing, 6 patients (50%) had a restrictive defect, 2 (17%) had airflow obstruction, and 4 (33%) had an isolated reduction in diffusing capacity of lung for carbon monoxide. The severity of emphysema ranged from mild to severe to focal bullae. All patients had chronic hypersensitivity pneumonitis (CHP). Centrilobular emphysema was most commonly seen with coexistent paraseptal emphysema in 5 patients. Emphysema was most frequent in the upper lung but could be seen in any lobe. Conclusion Emphysema can occur in patients with CHP independently of smoking history and exposure to specific types of antigens. Emphysematous changes seem to progress at a slower pace compare to reticulations/fibrosis.

Mycophenolate mofetil for scleroderma-related interstitial lung disease: A real world experience

Background and objective Interstitial lung disease (ILD) remains the number one cause of mortality in scleroderma (SSc). Our goal was to determine the effectiveness of mycophenolate mofetil (MMF) in treating SSc-ILD in a retrospective study. Methods A retrospective, computer-assisted search was performed to identify patients with SSc-ILD treated with MMF from 1997 through 2014. We used a novel software tool, Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER), to quantify parenchymal lung abnormalities on high-resolution computed tomography. Lung function was evaluated at baseline, 6, 12, and 24 months of MMF therapy. Results We identified 46 patients (28 females) with SSc-ILD (mean age at diagnosis 55 y) treated with MMF for at least 1 year (majority on 2 gm/day). Twenty-one patients (45.7%) stopped using MMF during the follow up period after the first 12 months, and they took MMF for a median of 2.12 years (range, 0.91–8.93 years). Only 4 discontinued MMF because of disease progression. Compared to baseline, the mean percentage change in forced vital capacity (95% CI) at 6, 12, and 24 months, respectively, was 1.01% (−2.38%-4.39%) (n = 26), 2.06% (−1.09%-5.22%) (n = 31), and −0.07% (−3.31%-3.17%) (n = 30), and the mean percentage change in ILD as measured by CALIPER (95% CI) was −5.40% (−18.62%-7.83%) (n = 18), −1.51% (−14.69%-11.68%) (n = 17), and −8.35% (−20.71%-4.02%) (n = 22).The mean right ventricular systolic pressure (RVSP) remained stable over the study period. Conclusions MMF is well tolerated and slows the rate of decline in lung function in SSc-ILD patients, even at doses lower at 3 g/day.

A 62-year-old man with dyspnea

We describe the case of a 62-year-old man who presented with shortness of breath that had progressed over several years. He had a history of a paralyzed right hemidiaphragm for at least the previous 10 years. He also reported weakness in his proximal legs and daytime sleepiness. On examination, he was found to have thoracoabdominal paradox when in supine position. Pulmonary function testing revealed severe restriction; arterial blood gas showed chronic respiratory acidosis. Electromyography showed chronic phrenic neuropathy bilaterally, with mild proximal myopathy. Serum aldolase level was mildly elevated, but serologic tests for connective tissue disorders were within reference range. After extensive clinical investigations, the patient was found to have severely reduced acid α-glucosidase. Genetic analysis confirmed the diagnosis of adult-onset Pompe disease. The patient started treatment with bilevel positive airway pressure titrated during polysomnography, and acid α-glucosidase enzyme replacement was recommended.

The Non-ILD Pulmonary Manifestations of RA

Pulmonary manifestations in RA can involve any of the intrathoracic compartments including the lung parenchyma, airways, pleura, and the pulmonary vasculature. Parenchymal lung disease consists of interstitial lung disease (ILD) and rheumatoid lung nodules. Rheumatoid lung nodules can be confused for malignancy. Airway diseases include cricoarytenoiditis, bronchiectasis, and small airway disease including constrictive bronchiolitis which can cause progressive airflow obstruction resulting in respiratory failure. Other forms of intrathoracic involvement include pleuritis, pleural effusion, and pulmonary vasculitis. In addition, drug-induced lung disease and pulmonary infections are relatively common in this patient population. Appropriate management of pulmonary disease in patients with RA depends on identifying the exact nature of the pulmonary involvement and its severity as well as the underlying cause and individual patient context.

Treatment of acute exacerbations of interstitial lung disease

ABSTRACT Introduction: Interstitial lung diseases (ILD) include a broad range of diffuse parenchymal lung disorders of known and unknown etiologies. Patients with ILD can experience acute exacerbations (AE) which are associated with extremely high morbidity and mortality. Little is known about the etiology of AEs, and whether inciting triggers (such as infection) result in an aberrant inflammatory response in a predisposed host. Areas covered: The majority of data regarding AE-ILD comes from the idiopathic pulmonary fibrosis (IPF) population and is extrapolated to other forms of ILD. For the purposes of this review we have summarized the current literature regarding AE of IPF, and when available have included data from AE of other ILDs. Expert commentary: Therapeutic options for AE are limited without definitive treatments available, and the prognosis is often poor. Treatment is mainly based on correcting hypoxemia, looking for reversible etiologies of respiratory decline, and palliation of symptoms. Overall little is known about the pathogenesis of ILDs and AE-ILD, more research is needed in hopes of identifying better treatment options.