Transbronchial Cryobiopsy in Immunocompromised Patients with Pulmonary Infiltrates: A Pilot Study

Background

In immunocompromised patients with pulmonary infiltrates, transbronchial lung biopsies (TBB) obtained by forceps has been shown to increase the diagnostic yield over simple bronchoalveolar lavage. Cryo-TBB is a novel modality for obtaining lung biopsies. We aimed to evaluate for the first time the efficacy and safety of cryo-TBB in immunocompromised patients.

Methods

Fifteen immunocompromised patients with pulmonary infiltrates underwent cryo-TBB. During the procedure two to three biopsy samples were taken. Procedure characteristics, complications, and the diagnostic yield were retrospectively evaluated.

Results

Most patients (n = 11) were immunocompromised due to hematological malignancies. The remaining four patients were receiving chronic immunosuppressive treatment due to previous solid-organ transplantation (n = 2) or collagen-vascular disease (n = 2). No major complications occurred in the cryo-TBB group. The mean surface area of the specimen taken by cryo-TBB was 9 mm². The increase in surface area and quality of biopsy samples translated to a high percentage of alveolated tissue (70 %) that enabled a clear histological detection of the following diagnoses: noncaseating granulomatous inflammation (n = 2), acute interstitial pneumonitis consistent with drug reaction (n = 5), nonspecific interstitial pneumonia fibrotic variant (n = 1), diffuse alveolar damage (n = 3), organizing pneumonia (n = 3), and pulmonary cryptococcal pneumonia (n = 1). Diagnostic information obtained by cryo-TBB led to change in the management of 12 patients (80 %).

Conclusion

Cryo-TBB in immunocompromised patients with pulmonary infiltrates provides clinically important diagnostic data with a low complication rate. These advantages should be further compared with traditional forceps TBB in a prospective randomized trial.     

DILI Associated with Skin Reactions

Purpose of Review

Adverse drug reactions (ADR) frequently involve the liver and skin in the form of drug-induced liver injury or cutaneous drug eruption.

Recent Findings

Skin ADR can range from harmless rash to severe skin manifestations such as drug rash with eosinophilia and systemic symptom syndrome (DRESS syndrome), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), all of which can be associated with severe outcome, including a 30% mortality rate in case of TEN. The association with co-occurring liver injury varies and in DRESS and SJS/TEN can contribute to substantial morbidity and mortality.

Summary

Liver and skin ADR are frequent but rarely severe; however, if severe, they are not uncommonly fatal.

     

Pulmonary Alveolar—Septal Amyloidosis Associated with Pulmonary Tuberculosis and an Unusual Paraproteinaemia

Summary: A patient is described who presented with mixed obstructive and restrictive lung disease, shown to be due to deposition of amyloid in an alveolar-septal distribution. An association with a plasma cell dyscrasia and pulmonary tuberculosis is discussed, as is the need for early diagnosis and a trial of aggressive cytotoxic therapy in primary amyloidosis.     

Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever

Chest symptoms and pleural effusion due to serositis in familial Mediterranean fever (FMF) are occasionally misdiagnosed as acute pneumonia. However, the actual pulmonary involvement of FMF is extremely rare. A 67-year-old man was referred to our hospital due to repeated and transient anterior chest pain. Chest images revealed a moderate amount of pericardial fluid, slight bilateral pleural effusion, and infiltrations in both lower lung lobes. Colchicine treatment without antibiotics rapidly improved these symptoms and findings. Pericarditis, pleurisy and the response to colchicine indicated FMF. FMF should be considered as a causative disease of pulmonary infiltrations, especially if it occurs repeatedly.     

Inhaled Treprostinil in Pulmonary Hypertension Associated with Lung Disease

Purpose

Pulmonary hypertension (PH) in the setting of parenchymal lung disease adversely affects quality of life and survival. However, PH-specific drugs may result in ventilation/perfusion imbalance and currently, there are no approved PH treatments for this patient population. In the present retrospective study, data from 22 patients with PH associated with lung disease treated with inhaled treprostinil (iTre) and followed up clinically for at least 3 months are presented.

Methods

PH was defined by resting right heart catheterization as a mean pulmonary artery pressure (mPAP) ≥?35 mmHg, or mPAP?≥?25 mmHg associated with pulmonary vascular resistance ≥?4 Woods Units. Follow-up evaluation was performed at the discretion of the attending physician.

Results

From baseline to follow-up, we observed significant improvement in functional class (n?=?22, functional class III-IV 82 vs. 59%, p?=?0.041) and 6-min walk distance (n?=?11, 243?±?106 vs. 308?±?109; p?=?0.022), without a deleterious effect on resting peripheral oxygen saturation (n?=?22, 92?±?6 vs. 94?±?4; p?=?0.014). Most of the patients (86%, n?=?19/22) were using long-term nasal supplemental oxygen at baseline. During follow-up, only one patient had increased supplemental oxygen requirement. The most common adverse events were cough, headache, and diarrhea. No severe adverse event was reported.

Conclusions

The results suggest that iTre is safe in patients with Group 3 PH and evidence of pulmonary vascular remodeling in terms of functional class, gas exchange, and exercise capacity. Additionally, iTre was well tolerated. The potential role of PH-specific drugs in Group 3 PH should be further assessed in larger prospective studies.

     

A Case of Alpha-Thalassemia-2 Associated with Pulmonary Infarction

Pulmonary infarction is an entity of medical significance that develops concurrently in beta-thalassemia but not in alpha-thalassemia. The reason for this difference is yet to be elucidated. We have evaluated a 21-year-old male alpha-thalassemia-2 patient who had profound microcytic anemia and pulmonary infarction. Analysis of the alpha-globin gene revealed -alpha3.7/alpha alpha genotype. His mother also had the same heterozygous gene deletion, though she had neither anemia nor pulmonary infarction. Since the patient had no other predisposition to pulmonary infarction, it is suggested that there is a close etiologic relationship between morphologic abnormality of the erythrocytes caused by alpha-thalassemia-2 and development of pulmonary infarction.     

Idiopathic Pulmonary Fibrosis is Associated with Circulating Antiepithelial Antibodies

Purpose

Idiopathic pulmonary fibrosis (IPF) is a restrictive fibrotic lung disease of uncertain etiology. Alveolar epithelial injury may be one of the inciting triggers in the pathogenesis of this disorder. We hypothesized that circulating antibodies to alveolar epithelial and endothelial cells may be involved in the pathogenesis of IPF.

Methods

Antibodies to alveolar epithelial and endothelial cells were analyzed by indirect immunofluorescence using alveolar epithelial cells (A549) and human umbilical vein endothelial cells respectively. IgG and IgM antibodies in patients’ serum were evaluated. Patterns of immunofluorescence, including membranous, cytoplasmic, and nuclear staining, were analyzed by fluorescence microscopy. The severity of immunofluorescence was divided into mild, moderate, and severe categories. Fifty-six patients (IPF?=?28, non-IPF ILD?=?9, non-ILD control?=?19) were evaluated for antiepithelial antibodies, and 28 patients (IPF?=?12, non-IPF ILD?=?3, non-ILD control?=?13) were studied for antiendothelial antibodies.

Results

Compared with control subjects, serum from IPF patients displayed significantly higher IgG binding to alveolar epithelial cells (P?=?0.041) with a membranous pattern of immunofluorescence. However, there was no significant difference in immunofluorescence with IgG on endothelial cells (P?=?0.165). In terms of IgM antibodies, there was no differential fluorescence observed for either epithelial or endothelial cells.

Conclusions

There is evidence of increased IgG antibodies directed against alveolar epithelium in IPF. These antibodies may play a significant role in the pathogenesis of this fibrotic disorder. The findings of this study suggest further evaluation of the role of immune mediated alveolar epithelial injury in IPF.     

Reversible Pulmonary Hypertension and Isolated Right-sided Heart Failure Associated with Hyperthyroidism

Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism.     

Zulu XX/XX Dispermic Chimaera from Natal with Two Populations of Red Blood Cells and Patchy Skin Pigmentation

The chimaera is female and has two children. Her blood contains 99% group O, type AcP:BA, Pep-A:8-2 and 1% group A2B, type AcP:RA, Pep-A:1 red cells. H-, A- and B-transferase activities were demonstrated in her serum. The level of the H enzyme activity is low but is at the lower end of the normal range for group O persons. The levels of the A and B enzymes are also low but are higher than expected in a person with 1% A2B red cells in the blood. The levels of the A and B enzymes indicate that tissues other than the chimaera's haemopoietic tissue carry her genetically A2B cell line and are contributing the corresponding transferases to her plasma. Gross patchy skin pigmentation is present on the upper part of her body. The chimaera has evidently inherited two dissimilar germ nuclei from each parent.