The Relationship Between Anti-SSA-52 and Interstitial Lung Disease.

OBJECTIVE: The aims of this study were to assess whether a relationship between anti-SSA-52 and interstitial lung disease (ILD) can be further defined, and to enhance screening, detection, and potentially guide treatment. METHODS: A historical cohort study of 201 patients was conducted at a single tertiary care center between January 1, 2016 and December 31, 2020. All included patients were anti-SSA-52 antibody positive. Chart review was performed for laboratory values, symptoms, pulmonary function tests, treatment, and imaging. Chest computed tomographies were reviewed by chest radiologists. RESULTS: Among anti-SSA-52 antibody-positive patients, ILD was found in 125 (62.2%) compared with 76 (37.8%) with no ILD (p = 0.001). For those with ILD, 78 (62.4%) were diagnosed with connective tissue disease (CTD)-associated ILD, 28 (22.4%) were diagnosed ILD only, and 19 (15.2%) met the criteria for interstitial pneumonia with autoimmune features. In patients with CTD-ILD, 18 (23.0%) had their ILD diagnosis made over 6 months before a CTD diagnosis, and an additional 43 (55.1%) had their ILD and CTD diagnosed within 6 months of each other (p < 0.001). Common computed tomography patterns were nonspecific interstitial pneumonia/organizing pneumonia overlap in 44 (35.2%), 25 (20.0%) nonspecific interstitial pneumonia, and 15 (12%) usual interstitial pneumonia. Twenty-eight (35.9%) had antisynthetase syndrome, followed by 16 (20.5%) with dermatomyositis, 10 (12.8%) with CTD overlap, and 6 (7.7%) with systemic scleroderma. CONCLUSIONS: There was a significant association between anti-SSA-52 antibodies and ILD across a wide spectrum of rheumatological diagnoses. A significant portion of patients were diagnosed with ILD either at the same time or before their CTD diagnosis. Further study will be needed to assess effective treatment and response.

Interstitial lung abnormalities after hospitalization for COVID-19 in patients with cancer: A prospective cohort study.

INTRODUCTION: Survivors of SARS-CoV-2 pneumonia often develop persistent respiratory symptom and interstitial lung abnormalities (ILAs) after infection. Risk factors for ILA development and duration of ILA persistence after SARS-CoV-2 infection are not well described in immunocompromised hosts, such as cancer patients. METHODS: We conducted a prospective cohort study of 95 patients at a major cancer center and 45 patients at a tertiary referral center. We collected clinical and radiographic data during the index hospitalization for COVID-19 pneumonia and measured pneumonia severity using a semi-quantitative radiographic score, the Radiologic Severity Index (RSI). Patients were evaluated in post-COVID-19 clinics at 3 and 6 months after discharge and underwent comprehensive pulmonary evaluations (symptom assessment, chest computed tomography, pulmonary function tests, 6-min walk test). The association of clinical and radiological factors with ILAs at 3 and 6 months post-discharge was measured using univariable and multivariable logistic regression. RESULTS: Sixty-six (70%) patients of cancer cohort had ILAs at 3 months, of whom 39 had persistent respiratory symptoms. Twenty-four (26%) patients had persistent ILA at 6 months after hospital discharge. In adjusted models, higher peak RSI at admission was associated with ILAs at 3 (OR 1.5 per 5-point increase, 95% CI 1.1-1.9) and 6 months (OR 1.3 per 5-point increase, 95% CI 1.1-1.6) post-discharge. Fibrotic ILAs (reticulation, traction bronchiectasis, and architectural distortion) were more common at 6 months post-discharge. CONCLUSIONS: Post-COVID-19 ILAs are common in cancer patients 3 months after hospital discharge, and peak RSI and older age are strong predictors of persistent ILAs.

Interstitial Lung Disease in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients: Comparison With Idiopathic Pulmonary Fibrosis.

BACKGROUND/OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may involve the kidney, respiratory tract, skin, or central and peripheral nervous system. Reports of interstitial lung disease (ILD) in AAV (AAV-ILD) have been increasing. METHODS: We reviewed the medical records of all patients with AAV-ILD between January 1, 2007, and December 31, 2017, and compared their pulmonary involvement to patients with idiopathic pulmonary fibrosis (IPF). RESULTS: We identified 24 patients with AAV-ILD: 14 with microscopic polyangiitis, 8 with granulomatosis with polyangiitis, and 2 with eosinophilic granulomatosis with polyangiitis. Perinuclear or myeloperoxidase ANCA was present in 16 cases (66.7%), whereas cytoplasmic or proteinase 3 ANCA was positive in 8 (33.3%). Usual interstitial pneumonia (UIP) was seen in 11 (45.8%), probable UIP in 1 (4.2%), indeterminate UIP in 2 (8.3%), and an alternate diagnosis in 10 (41.7%), and was further characterized as chronic hypersensitivity pneumonitis-like pattern seen in 6 (25%), nonspecific interstitial pneumonia-like pattern in 3 (12.5%), and cryptogenic organizing pneumonia-like pattern in 1 (4.2%). Forced vital capacity and diffusing capacity declined over time in patients with AAV-ILD. When compared with the IPF cohort, patients with AAV-ILD had intermediate survival and speed of lung function decline (3-year survival in AAV-ILD group was 94% vs 69% in IPF). CONCLUSIONS: Antineutrophil cytoplasmic antibody-associated vasculitis ILD is a progressive and potentially fatal condition. Although most cases in the literature are associated with p-ANCA and positive myeloperoxidase, we found that a third of patients had c-ANCA or granulomatosis with polyangiitis. Our cohort adds experience in this rare manifestation of AAV.

Central Airway Collapse, an Underappreciated Cause of Respiratory Morbidity.

Dyspnea, cough, sputum production, and recurrent respiratory infections are frequently encountered clinical concerns leading patients to seek medical care. It is not unusual for a well-defined etiology to remain elusive or for the therapeutics of a presumed etiology to be incompletely effective. Either scenario should prompt consideration of central airway pathology as a contributor to clinical manifestations. Over the past decade, recognition of dynamic central airway collapse during respiration associated with multiple respiratory symptoms has become more commonly appreciated. Expiratory central airway collapse may represent the answer to this diagnostic void. Expiratory central airway collapse is an underdiagnosed disorder that can coexist with and mimic asthma, chronic obstructive pulmonary disease, and bronchiectasis. Awareness of expiratory central airway collapse and its spectrum of symptoms is paramount to its recognition. This review includes clear definitions, diagnostics, and therapeutics for this challenging condition. We performed a narrative review through the PubMed (MEDLINE) database using the following MeSH terms: airway collapse, tracheobronchomalacia, tracheomalacia, and bronchomalacia. We include reports from systematic reviews, narrative reviews, clinical trials, and observational studies from 2005 to 2020. Two reviewers evaluated potential references. No systematic reviews were found. A total of 28 references were included into our review. Included studies report experience in the diagnosis and/or treatment of dynamic central airway collapse; case reports and non-English or non-Spanish studies were excluded. We describe the current diagnostic dilemma, highlighting the role of dynamic bronchoscopy and tracheobronchial stent trial; outline the complex therapeutic options (eg, tracheobronchoplasty); and present future directions and challenges.

A 64-Year-Old Man With Rapidly Progressive Respiratory Failure and Pneumomediastinum.

CASE PRESENTATION: A 64-year-old man presented for consideration for lung transplant. He had a history of previous tobacco use, OSA on CPAP therapy, and gastroesophageal reflux disease. He worked as a design engineer. The patient had a 4-year history of dyspnea on exertion, followed with periodic CT scan of the chest. Nine months prior to his evaluation for lung transplant, the patient developed worsening of dyspnea, dry cough, poor appetite, and weight loss. At times, the cough was violent and associated with chest pressure. He was prescribed systemic corticosteroids and antibiotics without improvement. Four months later, the patient noted sudden onset of severe chest pain and worsening dyspnea. A CT scan of the chest demonstrated extensive pneumomediastinum in addition to changes consistent with pulmonary fibrosis. An esophagogram showed thickening of the distal esophagus, but no signs of perforation. He was prescribed supplemental oxygen and advised to stop the use of CPAP. The patient sought a second opinion. A CT scan of the chest showed improvement of the pneumomediastinum and extensive fibrotic lung disease. Pulmonary function tests (PFTs) were consistent with a restrictive pattern, decreased diffusing capacity (Dlco), and a preserved residual volume over total lung capacity ratio. The patient was prescribed systemic corticosteroids with no improvement of his symptoms. Repeat PFTs showed further decline of Dlco, and he was referred for lung transplant evaluation.

Interstitial Lung Disease and Other Pulmonary Manifestations in Connective Tissue Diseases.

Lung involvement in connective tissue diseases is associated with substantial morbidity and mortality, most commonly in the form of interstitial lung disease, and can occur in any of these disorders. Patterns of interstitial lung disease in patients with connective tissue disease are similar to those seen in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis. It may be difficult to distinguish between the 2 ailments, particularly when interstitial lung disease presents before extrapulmonary manifestations of the underlying connective tissue disease. There are important clinical implications in achieving this distinction. Given the complexities inherent in the management of these patients, a multidisciplinary evaluation is needed to optimize the diagnostic process and management strategies. The aim of this article was to summarize an approach to diagnosis and management based on the opinion of experts on this topic.

Interstitial lung disease in patients with mixed connective tissue disease: pilot study on predictors of lung involvement.

OBJECTIVES: Mixed connective tissue disease (MCTD) is an immune-mediated systemic disorder characterised by serum autoantibodies against U1-ribonucleoprotein and diverse multisystemic clinical manifestations. Approximately 50% of patients with MCTD develop a radiologic pattern of interstitial lung disease (ILD). Our single centre, cross-sectional study sought to identify clinical and serologic associations of ILD in patients with MCTD which may serve as predictors of lung disease and prognosis. METHODS: Patients who met validated criteria for diagnosis of MCTD were included in the study, and were further differentiated into study and control groups based on presence or absence of ILD. RESULTS: Multivariate logistic regression showed an association of two clinical variables: dysphagia with an R2 value of 0.33 (p-value <0.001) and Raynaud's phenomenon with R2 value of 0.28 (p-value <0.001). CONCLUSIONS: An association of dysphagia with the development of ILD in our study is in harmony with the existing literature. There are primarily case reports, suggesting an association of Raynaud's phenomenon with development of ILD in patients with undifferentiated CTD. To our knowledge, this is the first study highlighting the association of Raynaud's phenomenon with development of ILD in patients with MCTD. The mechanistic aspects of the association between Raynaud's phenomenon and ILD remain unexplored. The association of easily elicited historical and clinical features of MCTD with subtle, but worrisome, pulmonary pathology carries the promise of sensitising the unsuspecting clinician about the entity of ILD in MCTD.

Multidisciplinary Perioperative Management of Pulmonary Arterial Hypertension in Patients Undergoing Noncardiac Surgery.

OBJECTIVES: To describe the effect of implementing a contemporary perioperative pulmonary hypertension (PH)-targeted protocol in patients with pulmonary arterial hypertension (PAH) undergoing noncardiac surgery (NCS). METHODS: The data of consecutive patients with PAH diagnosed by right heart catheterization who underwent NCS between January 1, 2006 and February 9, 2016 were reviewed. Patient demographics, etiology of PAH, clinical features, diagnostic data, utilization of PH-specific medications, and trend of perioperative complications rate were recorded during the study period. RESULTS: In the base cohort of 375 patients, 37 had NCS. The mean age at surgery was 62 years. Most patients were women (78%) classified in group 1 PAH. At the time of the surgery, 86% were New York Heart Association functional class III/IV and 97% had American Society of Anesthesiologists classifications 3 and 4. A larger proportion of patients displayed lower PAH risk scores between 2006 and 2011 (P = 0.045). Conversely, a higher percentage of patients exhibited moderately high to very high PAH risk scores between 2012 and 2016 (P = 0.003). Perioperative and anesthetic-related morbidity was 27%, and no difference was observed between either period (P = 0.944). Most of the complications (70%) were related to general anesthesia. Two deaths (5%) occurred in our study group, both during the 2006-2011 period. CONCLUSIONS: The combination of a multidisciplinary perioperative approach, utilization of novel pulmonary vascular disease-targeted therapy, adequate perioperative optimization, and thoughtful selection of anesthetic technique seems to be a potential strategy to at least maintain similar perioperative outcomes among higher- and lower-risk patients with PAH undergoing NCS.

Nocardia brasiliensis Infection Complicating Cryptogenic Organizing Pneumonia.

Pulmonary nocardiosis is a severe and uncommon opportunistic infection caused by Nocardia species. We present a patient with cryptogenic organizing pneumonia who was receiving long-term immunosuppressive therapy, whose treatment course was complicated by cutaneous and pulmonary nocardiosis. Tissue cultures confirmed Nocardia brasiliensis. Nocardiosis should be a diagnostic consideration for patients treated with long-term immunosuppression who have worsening pulmonary symptoms and relapsing pustular skin lesions.

Etiologies of consecutive series of non-necrotizing granulomas.

Background: Sarcoidosis is an idiopathic granulomatous disease characterized by variable organ involvement and non-necrotizing granulomas. Objectives: To determine how often non-necrotizing granulomas are not secondary to sarcoidosis. Methods: A retrospective review was conducted to evaluate all biopsies performed at Mayo Clinic in Jacksonville, Florida from January 1, 1996, to December 31, 2013, showing non-necrotizing granulomas. Results: Three hundred and eight biopsies showing non-necrotizing granulomas met inclusion criteria. The average age was 58.2 years, 60.7% were female, and 85% were Caucasian. The most common symptoms were pulmonary (74.6% of cases), and the most common objective finding was lymphadenopathy (33.8%). The organs biopsied included lung parenchyma (65.3%), intrathoracic lymph nodes (25%), other lymph nodes (1.6%), liver (1.3%), airway (1.3%), skin (1.3%), kidney (0.7%), bone marrow (0.7%), gastrointestinal (0.7%), and one each from the brain, heart, bone, bladder, spleen, tendon, and eye. The suspected diagnosis was confirmed in 224 cases (72.7%). From the remaining 84 cases (27.3%), suspected sarcoidosis was refuted in 9, the initial diagnosis was changed to sarcoidosis in 37 (44%), and in 38, it was changed to a different diagnosis. Sarcoidosis was the final diagnosis in 173 (56%). Conclusion: Sarcoidosis was the leading cause of non-necrotizing granulomas, but in 44% of cases, there was an alternate diagnosis. We estimate that more than a quarter of the initial diagnoses will be changed based on biopsy results and clinical course. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 115-121).

Dementia, gait disturbance, and urinary incontinence in a patient with pulmonary sarcoidosis.

Hydrocephalus is an uncommon presentation of neurosarcoidosis. We discuss the case of a 67-year-old woman with a prior diagnosis of hypothyroidism, systemic hypertension, and lung sarcoidosis who presented with a 1-month history of progressive impairment of consciousness leading to prostration and loss of sphincter control. At admission, patient was febrile with altered speech and without focalization. Laboratory results showed leucocytosis and mild anaemia. Cerebrospinal fluid (CSF) analysis was characterized by mild elevated protein level, increased cell count, normal glucose and adenosine deaminase (ADA), negative cytology, and no bacterial isolations. Electroencephalogram showed toxic-metabolic encephalopathy. Computed tomography (CT) of the brain revealed hydrocephalus without structural damage, and magnetic resonance imaging of the brain demonstrated non-specific diffuse meningeal enhancement and periventricular changes supporting normal pressure hydrocephalus. Chest X-ray showed mediastinal adenopathy and parenchymatous lesions, consistent with stage II lung sarcoidosis. A ventriculoperitoneal shunt was installed, and the patient experienced rapid improvement in her symptoms.

Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed connective tissue disease.

Interstitial lung disease is a common and often life-threatening manifestation of different connective tissue disorders, often affecting its overall prognosis. Systemic lupus erythematosus, Sjögren syndrome, and mixed connective tissue disease, although all unique diseases, can have lung manifestations as an important part of these conditions. This article reviews the different pulmonary manifestations seen in these 3 systemic rheumatologic conditions.

Pulmonary Vein Stenosis Mimicking Nonspecific Interstitial Pneumonia.

Pulmonary vein stenosis (PVS) is a known complication after catheter ablation of arrhythmias. Surprisingly, little information is available on its manifestations in the lung. We describe the case of a 39-year-old woman who presented from an outside hospital with worsening shortness of breath after catheter ablation of pulmonary veins for atrial fibrillation. After an initial diagnosis of pneumonia and its nonimprovement with antibiotics, a surgical lung biopsy was done and interpreted as nonspecific interstitial pneumonia (NSIP) with vascular changes consistent with pulmonary arterial hypertension. Later, she was admitted to our institution where a transthoracic echocardiogram (TTE) and subsequent computed tomography (CT) angiogram of the heart showed severe stenosis of all four pulmonary veins. The previous lung biopsy was rereviewed and reinterpreted as severe parenchymal congestion mimicking NSIP. Our case demonstrates that PVS is an underrecognized complication of catheter ablation, and increased awareness among both clinicians and pathologists is necessary to avoid misdiagnosis.

A 40-year-old woman with multiple pulmonary nodules. Pulmonary hyalinizing granuloma.

A 40-year-old woman (a nonsmoker) with history of idiopathic thrombocytopenic purpura and a platelet count > 90,000 cells/µL without specific medication was referred to pulmonary clinic for evaluation of multiple pulmonary nodules. The patient presented to an outside hospital with fatigue, lack of energy, and dyspnea on exertion for 2 years. She denied fever, cough, chest pain, or weight loss. An initial chest radiograph showed bilateral multiple pulmonary nodules. A chest CT scan revealed multiple nodular lesions, varying in size, in all lobes of both lungs. There was no mediastinal lymphadenopathy or pleural effusion. There was no significant hypermetabolic activity on a subsequent fluorodeoxyglucose PET scan/CT scan, and there had been no significant change. She underwent CT scan-guided percutaneous transthoracic biopsy and bronchoscopy with transbronchial biopsies, all of which were inconclusive. An open lung biopsy was considered.

A retrospective review of clinical features and treatment outcomes in steroid-resistant interstitial lung disease from polymyositis/dermatomyositis.

INTRODUCTION: We reviewed our experience with immunosuppressive agents in patients with steroid-resistant Interstitial Lung Disease in the setting of Polymyositis/Dermatomyositis (PM/DM-ILD) to determine whether there were major differences in outcomes. METHODS: We identified all patients treated for PM/DM-ILD and assessed cyclophosphamide (CYC), azathioprine (AZA) and mycophenolate (MMF) when used as first-line steroid sparing therapy for effects on pulmonary function variables, dyspnea and tolerance at six and twelve months. RESULTS: Among 46 patients meeting the inclusion criteria, 24 were treated with CYC, 13 with AZA and 9 with MMF. There were no baseline differences between the three treatment groups for any of the demographic or physiologic variables, dyspnea score, the presence of >30% fibrosis on CT, or the baseline steroid dose. At the six months assessment, the overall median change in FVC was 5.0% (25th, 75th percentile -3, 11.5%), corresponding to +.20 L (.09, 0.42 L) and the DLCO increased by 2.93% (-4, 9%), corresponding to 1 mm/ml/Hg (-.58, 2.3). The severity of dyspnea decreased substantially, prednisone dose could be reduced and no important difference in side effects was found in the whole group of patients. This effect was sustained after twelve months of therapy. CONCLUSIONS: In patients with PM/DM-ILD related, treatment with CYC, AZA or MMF was associated with stabilization of pulmonary physiology, improved dyspnea, and a reduction of steroid dose.

Mucosa-associated lymphoid tissue lymphoma of the trachea.

Primary malignant lymphoma of the trachea is rare. We report a case of a 60-year-old woman with a mucosa-associated lymphoid tissue lymphoma of the trachea and review the existing literature. This case highlights the importance of including intraluminal lesions in the differential diagnosis when a variable degree of obstruction is seen on pulmonary function testing.