Chronic Interstitial Pneumonitis Research Articles

Canine Visceral Leishmaniasis: A Histological and Immunohistochemical Study of Fibropoiesis in Chronic Interstitial Pneumonitis.

We studied some fibrotic aspects of chronic interstitial pneumonitis in the lungs of dogs infected with Leishmania infantum. The lungs of eleven naturally infected dogs, twelve experimentally infected with two distinct strains of L. infantum (BH401 and BH46), and six uninfected (controls) dogs, were analyzed by histological, parasitological, and immunohistochemical studies. Conventional histology (HE), collagen deposition (Gomori's silver staining for reticulin collagen fibers), and immunohistochemistry for myofibroblast characterization were carried out based on the cellular expression of alpha-smooth muscle actin, vimentin, cytokeratin, E-cadherin, snail antigen homologue 1 (SNAI1) (Snail), and the cytokine expression of transforming growth factor-beta (TGF-β). Parasitological screening was carried out using conventional polymerase chain reaction (PCR) and the immunohistochemical reaction of streptavidin-peroxidase for visualizing Leishmania amastigotes. Dogs naturally infected with L. infantum and experimentally infected with L. infantum BH401 strains showed intense interstitial pneumonitis characterized by thickening of the alveolar septa as a consequence of an intense diffuse and focal (plaques) chronic exudate of mononuclear cells associated with fibrogenesis. The expression of alpha-actin, vimentin, and TGF-β was higher in the lung interstitium of all infected dogs than in the other two groups (BH46 strain and controls). Moreover, in both the naturally and experimentally infected dog (BH401 strain) groups, the expression of Snail was moderate to intense in contrast to the other groups. Based on these immunohistochemical results, we concluded that mesenchymal cells are active in promoting changes in the extracellular matrix in the lungs of dogs naturally and experimentally infected with L. infantum, but it depends on the virulence of the parasite.

Managing Spontaneous Pneumothorax.

Pneumothorax is commonly cared for in the emergency department, with an incidence ranging from 6 to 66 per 100,000 per year1-4 and a 1-year recurrence rate of 29%.5 It is more common in men and has a biphasic distribution occurring more frequently in the 15 to 30-year-old and ≥65-year-old groups.1-4 Risk factors include chronic obstructive pulmonary disease, asthma, interstitial pneumonitis, cystic fibrosis, tuberculosis, lung cancer, and smoking history.1,4,6-10 Pneumothorax can be qualified as traumatic or spontaneous (ie, atraumatic).

A 5-year follow-up of pulmonary function tests in childhood-onset systemic lupus erythematosus: a single-center retrospective study.

Pulmonary involvement in childhood-onset systemic lupus erythematosus (cSLE), contributes to significant morbidity and mortality. Manifestations include chronic interstitial pneumonitis, pneumonia, pleuritis, alveolar hemorrhage, and shrinking lung syndrome. However, many patients can be asymptomatic from a respiratory standpoint and still have pulmonary function test (PFT) abnormalities. Our aim is to describe PFT abnormalities in patients with cSLE. We completed a retrospective review of 42 patients with cSLE followed at our center. These patients were at least 6 years old (so they could complete PFTs). We collected data from July 2015 to July 2020. Out of the 42 patients, 10 (23.8%) had abnormal PFTs. These 10 patients had a mean age at diagnosis of 13 ± 2.9 years. Nine were female. One-fifth (20%) self-identified as Hispanic, 20% as Asian, 10% as Black or African American, and the remaining 50% as "Other." Of the 10, 3 had restrictive disease only, 3 with diffusion impairment only, and 4 with both restrictive lung disease and diffusion impairment. Patients with restrictive patterns had a mean total lung capacity (TLC) of 72.5 ± 5.8 throughout the study period. The average diffusing capacity for carbon monoxide corrected for hemoglobin (DsbHb) among patients with diffusion limitation during the study period was 64.8 ± 8.3. The most common PFT abnormalities seen in patients with cSLE are alterations in diffusing capacity as well as restrictive lung disease.

Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia.

The prognosis of idiopathic chronic fibrotic interstitial pneumonitis (CFIP) in patients with acute exacerbation (AE) is variable. We examined whether the imaging pattern on thoracic computed tomography (CT) or the severity of respiratory failure with AE-CFIP is associated with short-term prognosis. Patients admitted to two university hospitals were retrospectively analyzed and divided into derivation and validation cohorts. The distribution of newly appearing parenchymal abnormalities on thoracic CT was classified into peripheral, multifocal, and diffuse patterns. Respiratory failure was defined as severe if a fraction of inspired oxygen ≥ 0.5 was required to maintain percutaneous oxygen saturation ≥ 90% on admission. Factors associated with 90 day-mortality were analyzed using univariate and Cox proportional hazard regression. In 59 patients with AE-CFIP of the derivation cohort, diffuse pattern on CT was associated with higher mortality within 90 days (43%) than peripheral/multifocal pattern (17%, p = 0.03). Additionally, compared with non-severe failure, severe respiratory failure was associated with higher mortality (47% vs. 21%, p = 0.06). Cox proportional hazard regression analysis demonstrated that a combination of diffuse pattern on CT and severe respiratory failure was associated with the poorest prognosis (hazard ratio [HR] 3.51 [interquartile range 1.26-9.80], p = 0.016) in the derivation cohort, which was confirmed in the validation cohort (n = 31, HR 4.30 [interquartile range 1.51-12.2], p = 0.006). The combination of imaging pattern on thoracic CT and severity of respiratory failure was associated with the prognosis of idiopathic AE-CFIP.

Impact of beta blockers on resting respiratory rate in older adults: A cross-sectional study

[Purpose] Beta blockers, commonly prescribed for older adults, affect heart rates and blood pressure and may reduce respiratory rates, which are used to evaluate patient status and predict outcomes. However, limited clinical evidence is available on the impact of beta blockers on respiratory rates. This study aimed to investigate the impact of beta blockers on respiratory rates in older adults.[Methods] This cross-sectional study included patients aged ≥60 years who underwent an annual checkup. Patients were excluded if they had a diagnosis of severe heart failure, chronic obstructive pulmonary disease, interstitial pneumonitis, severe anemia, or neurodegenerative disease. Doubly robust estimation with inverse probability weighting was applied to estimate the mean differences between beta blocker users and non-users. The dose-response relationship between the administered beta blockers and respiratory rates was examined using multivariable regression models.[Results] Of 637 participants, 108 had received beta blockers regularly. The adjusted mean differences (95% confidence interval, CI) in respiratory rates, pulse rates, systolic blood pressure, and diastolic blood pressure between beta blocker users and non-users were 0.35 (−0.68 to 1.37), −3.56 (−6.34 to −0.78), −5.53 (−8.53 to −2.52), and −4.70 (−8.27 to −1.14), respectively. The adjusted mean differences (95% CI) in respiratory rates per 1 mg of a carvedilol equivalent dose in all beta blocker users, liposoluble beta blocker users, and carvedilol users were −0.10 (−0.18 to −0.02), −0.35 (−0.59 to −0.11), and −0.29 (−0.54 to −0.06), respectively.[Conclusions] Beta blockers may dose-dependently reduce the respiratory rates of older adults. However, in clinical settings, the impact of beta-blocker use or non-use on the respiratory rate may not occur at a clinically important level. Clinicians should note the potentially suppressive impact of beta blockers on respiratory rates according to the situation.

Isolated pulmonary langerhans cell histiocytosis: A diagnostic challenge in oncologic patients.

Isolated pulmonary langerhans cell histiocytosis: A diagnostic challenge in oncologic patients.

Long-Term Adverse Events of Total Marrow Irradiation (TMI)-Based Conditioning Chemotherapy in Hematopoietic Stem Cell Transplant Recipients Treated on a Phase I/II Trial

Hematopoietic stem cell transplant (HSCT) remains a curative option for many hematologic malignancies. However, disease relapse is still one of the major causes of death after transplant. Increasing the intensity of conditioning regimens may elicit more antitumor activity but not without additional risk of transplant-related morbidity and mortality. The use of total body irradiation (TBI), while it can be effective, carries the risk of long-term toxicity to extramedullary organs, as well as secondary cancers. We have previously demonstrated that the combination of myeloablative chemotherapy with intensity-modulated radiation therapy to the bone marrow, or TMI, delivered with a linear accelerator, does not increase the toxicity of transplant in the first year of follow up (PMID 29065747; PMID 25234438). However, the effects of TMI in long term survivors after hematopoietic stem cell transplant (HSCT) has not yet been described. In this study, we retrospectively analyzed 24 consecutive patients who received HSCT with a TMI-based conditioning regimen between 2014 and 2021. The median age was 55.5 (range: 20-70) years. The median post-transplant follow up was 37.8 (range 12.0-89.7) months. Of 24 patients, 9 were diagnosed with multiple myeloma (MM) and received an autologous HSCT conditioned with high-dose Melphalan combined with either 3 (n=3), 6 (n=1) or 9 (n=5) Gy TMI. 15 (10 with acute myeloid leukemia, 3 with myelodysplastic syndrome and 2 with chronic myeloid leukemia) received an allogeneic HSCT from either a matched or 1-antigen mismatched related or unrelated donor, combining TMI 9 Gy with myeloablative fludarabine-IV busulfan. We then analyzed the incidence adverse events reported in published studies of TBI-based HSCT in our patient population (Table 1). In our long-term HSCT survivors receiving TMI-based conditioning, we observed xerostomia in 9 cases (37%, 3 of which had eating impairment), osteopenia or osteoporosis in 8 (33%, 2 of which also had fractures), dental in 29% and cataracts in 29%. Three subjects developed chronic kidney disease (12.5%, 2 patients developed stage 3 and 1 developed stage 4), 2 developed hypothyroidism (8%) and 2 patients developed heart failure (8%, both with mild decrease in ejection fraction without clinical decompensation). Only one patient (4%) developed a secondary malignancy (T-large granular lymphocytic leukemia). One patient (4%) developed a chronic interstitial pneumonitis, which was of unclear etiology and resolved spontaneously, but severe enough to require oxygen. These rates were overall lower than those historically reported with TBI (PMID 29482775) and can also be attributed to the standard chemotherapy utilized in the conditioning regimens. In conclusion, TMI is a relatively safe treatment modality when included in myeloablative conditioning regimens for HSCT. The adverse events profile in our patient population was similar to that of TBI but with lower incidence rates for the majority of reported events. Phase 2 clinical trials using TMI in conditioning regimens are currently underway to assess HSCT outcomes and should guide its future use in HSCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Histological and Immunohistochemical Study of Chronic Interstitial Pneumonitis Fibrosis in Canine Visceral Leishmaniasis

Histological and Immunohistochemical Study of Chronic Interstitial Pneumonitis Fibrosis in Canine Visceral Leishmaniasis

AN UNUSUAL PRESENTATION OF CHRONIC COUGH: PLASTIC BRONCHITIS AND CHYLOPTYSIS

SESSION TITLE: Fellows Cardiothoracic Surgery Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Plastic bronchitis and chyloptysis are rare medical conditions characterized by expectoration of bronchial cast and production of white milky sputum rich in chyle, respectively. Plastic bronchitis is associated with congenital heart disease in children and lymphatic system disease in adults. CASE PRESENTATION: A 49-year-old Hispanic female with no past medical history presented with dyspnea and right-sided pleuritic chest pain during her first pregnancy 27 years ago. Initial evaluation, work up and imaging studies revealed right-sided chylothorax requiring chest tube placement, thoracotomy with decortication, and thoracic duct ligation. One month later, cisterna chyli ligation and right lower lobe wedge resection were performed. Right lower lobe biopsy results disclosed chronic interstitial pneumonitis and focal foreign body reaction. During follow up patient reported resolution of symptoms. In May 2019, the patient presented to our institution with four-month history of dyspnea, dry cough, and expectoration episodes of a thick, white-red, cord-like material accompanied by viscous milky white sputum. The patient’s symptoms progressively worsened where she developed a choking sensation at night and in supine position. Chest CT scan show small areas of ground glass airspace opacity in the dependent portions of bilateral lungs with concentric thickening of the right pleura. Bronchoscopy was performed and was notable for milky-white secretions with abundant pale and slightly red, stranded bronchial casts lodged within the left lower lobe anterior segment. Bronchial lavage and aspiration specimen sent for oil red stain showed macrophages with lipid droplets. These findings were consistent with the clinical impression of chyloptysis producing subsequent plastic bronchitis. Cytology was negative for malignancy. Patient completed course of broad spectrum antibiotics and steroids with partial improvement in her condition. She currently is under evaluation for embolization and/or invasive approach. DISCUSSION: This case addresses a 49-year-old female who presented with milky-white sputum and cough. Bronchoscopy showed milky-white secretions and bronchial cast, bronchial lavage was positive for oil red stain which confirms chyloptysis causing plastic bronchitis. She completed a course of antibiotics and steroids with partial improvement in her condition. Now is under evaluation for embolization and/or invasive approach. CONCLUSIONS: This case illustrates an unusual presentation of chronic cough and chyloptysis, confirmed by bronchoscopy. Plastic bronchitis and chyloptysis rare medical conditions that should be suspected after obtaining thorough history and physical exam, high index of suspicion is fundamental for the recognition and treatment of this rare entity. Reference #1: Itkin M, Mccormack FX, Dori Y. Diagnosis and Treatment of Lymphatic Plastic Bronchitis in Adults Using Advanced Lymphatic Imaging and Percutaneous Embolization. Annals of the American Thoracic Society. 2016;13(10):1689-1696. Reference #2: Lim KG, Rosenow EC, Staats BS, Morgenthaler TI. Chyloptysis in Adults: Presentation, Recognition, and Differential Diagnosis. Chest. 2004; 125:336-304. Reference #3: Stoddart A, Dincer HE, Iber C, Tomic R, Bhargava M. Chyloptysis causing plastic bronchitis. Respiratory Medicine Case Reports. 2014; 13:4-6. DISCLOSURES: No relevant relationships by Michael Cruz, source=Web Response No relevant relationships by Ricardo Fernandez, source=Web Response No relevant relationships by Giovanni Veloz Irizarry, source=Web Response

Disseminated Bacillus Calmette\u2013Gu\xe9rin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review

BackgroundIntravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.Case presentationA 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.ConclusionsWe report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Self-Assemble Amphiphilic PEO-PPO-PEO Tri-Block Co-Polymeric Methotrexate Nanomicelles to Combat MCF7 Cancer Cells.

Methotrexate (MTX) is a water-insoluble, anti-tumor agent that causes adverse effects like bone marrow suppression, chronic interstitial obstructive pulmonary disease, hepatotoxicity, leukopenia, interstitial pneumonitis and nephrotoxicity with slow drug release rate. The present study aimed to successfully incorporate MTX into novel-targeted Pluronic (PEOPPO- PEO tri-block co-polymer) F127 polymeric micelles intended for intravenous administration with improved drug loading and sustained release behavior necessary to achieve better efficacy of MTX. MTX-loaded Pluronic F127 micelles were characterized for critical micelle concentration, particle size and zeta potential,1H NMR, drug loading, encapsulation efficiency characterization, cell uptake, in vitro release study along with partition coefficient and solubilization thermodynamics. The micellar formulation resulted in nano size 27.32±1.43nm of PF127/SDS, as compared to Pluronic F127 micelles or PF127/Phosphatidyl choline which were 30.52±1.18nm and 154.35±5.5nm in size, respectively. The uptake of PF127/SDS micellar formulation incorporating Rhodamine 123 in MCF7 cancer cells was found to be higher (84.25%) than PF127/PC, PF127 and MTX i.e. 66.26%, 73.59% and 53% respectively. The in vitro MTX release from PF127, PF127/SDS and PF127/PC polymeric micelles formulations was observed to be 69%, 69.5% and 66% at 12 h whereas 80.89%, 77.67% and 78.54% after 24 h, respectively and revealed a sustained release. MTX-loaded PF127/SDS micelles showed high partition coefficient and negative free energy of solubilization compared to PF127 and PF127/PC which signify self-assembly behavior and thermodynamic stability towards higher dissociation. It was finally concluded that MTX-loaded PF127/SDS micelles act as a potential anticancer delivery system in comparison to PF127/PC and PF127 to combat tumor cells by enhancing their cellular uptake targeting with sustained release pattern and reducing the thermodynamic instability. Thus, PF127/SDS micellar formulation can provide a useful alternative dosage form for intravenous administration of MTX.

Risk factors of interstitial lung diseases in clinically amyopathic dermatomyositis.

BackgroundClinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.MethodsIn this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP).ResultsIn 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP.ConclusionsThis study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD.

Pulmonary hypertension due to interstitial lung disease.

Pulmonary hypertension has been reported to complicate the course of a number of fibrotic lung diseases, including idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis and nonspecific interstitial pneumonitis. Most commonly, mild elevations in the mean pulmonary artery pressure are seen in patients with advanced pulmonary fibrosis. However, some patients may develop severe pulmonary hypertension, which appears out of proportion to the degree of their restrictive lung disease. The benefits of pulmonary vasodilator therapy have yet to be established in pulmonary hypertension complicating fibrotic lung disease. In fact, one recent clinical trial examining riociguat in patients with pulmonary hypertension complicating idiopathic interstitial pneumonias was terminated early for an increased risk of death or hospitalization. Multiple clinical trials on this topic are currently ongoing, including studies examining inhaled pulmonary vasodilator therapies. The development of pulmonary hypertension is associated with increased exertional oxygen requirements, worsened functional capacity and attenuated life expectancy. It is hoped that continued research will find an effective therapy for this condition, which will improve quality of life and extend life expectancy in patients with this condition.

Role of novel synbiotic supplementation on ovalbumin induced allergy model: Impact on immunemodulation

This study aimed to determine effect of a novel synbiotic formulated from green gram on allergen induced immune response. BALB/c mice (F0 generation) were supplemented with saline, Lactobacillus rhamnosus GG (LGG) or synbiotic. The supplementation was continued throughout gestation and lactation. F1 generation pups also received respective supplementations as their mothers and were designated as postweaning probiotic and synbiotic groups. At the age of 60 days, OVA (allergen) sensitization was induced in F1 pups and various immune parameters were determined. As expected, OVA sensitized pups (F1 Ova+) developed chronic interstitial pneumonitis (CIP), with positive passive cutaneous anaphylaxis (PCA) reaction, increased (p < 0.05) specific and total IgG and IgE concentration along with higher (p < 0.05) allergenic IL-5 value (283.6 ± 11.8 pg/ml). Synbiotic supplementation among the offspring showed better protection against allergy in the pups, as observed by absence of CIP, negative PCA reaction and reduced (p < 0.05) IL-5 concentration (37.8 ± 2.42 pg/ml) compared to F1 Ova+ group. Probiotic supplementation showed similar protection from allergy although, synbiotic scored better as immunemodulator. Synbiotic treatment improved T-regulatory cells percentage by 4-fold whereas probiotic supplementation improved it by 3-fold compared to control. Synbiotic group had enhanced production of IL-10, TGF-β (p < 0.05) by 11.6-fold and 4-fold respectively, while probiotic group registered 9-fold and 3.65-fold increase respectively. Similarly, allergen specific IgG and IgE concentration reduced by 1.9 and 1.7-folds with synbiotic and probiotic supplementations respectively. In conclusion, synbiotic group scored better in preventing ovalbumin induced allergy compared to probiotic group among offspring when supplemented prenatally and postweaning.

Role of Transbronchial Biopsy in Diagnosis of Sirolimus-Associated Lung Toxicity in Solid Organ Transplant Patients

SESSION TITLE: Transplant SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: mTOR inhibitors play an integral role in induction and long-term maintenance immunosuppressive regimens used in solid organ transplant. However, sirolimus has been associated with a spectrum of lung toxicities, including interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia and diffuse alveolar hemorrhage, with estimated incidence 4.3-10%. Evidence suggests sirolimus possess proinflammatory effects resulting in exposure of cryptic pulmonary antigens, which leads to interstitial pneumonitis, lymphocytic alveolitis and alveolar hemorrhage. There is scant literature on describing transbronchial biopsy (TBB) patterns in the setting of sirloimus toxicity. This study aims to identify role of TBB in patients with suspected sirolimus-associated lung toxicity. METHODS: We identified patients who are on sirolimus as part of immunosuppressive regimen for solid organ transplant at our center between January 1999 and March 2013. Thirteen patients developed lung toxicity. We retrospectively screened patients who underwent TBB under conventional fluoroscopic guidance as part of the workup for sirolimus-associated lung toxicity. Pathology reports were reviewed for histological features. RESULTS: Thirteen patients with solid organ transplant were identified with suspected sirolimus-associated lung injury (10 kidneys, 1 kidney-pancreas, 1 liver and 1 heart). The mean age of patients was 62.4±10.9 years with male predominance (69%). TBB was performed in 10 patients. Mean time between starting sirolimus and TBB was 4.8±3.7 years. Trough blood sirolimus levels measured at time of TBB were supratherapeutic with mean 12.4±7.9 µg/L. The two prominent histological patterns were chronic interstitial pneumonitis (Figure 1) and focal organizing pneumonia (Figure 2). Rare multinucleated giant cells, lymphoplasmacytic infiltrates, fibrinous exudate and patchy interstitial fibrosis were noted as well. TBB revealed no evidence of malignancy, granulomas or infectious organisms. CONCLUSIONS: TBB should be given a strong consideration as part of workup for sirolumus-associated lung toxicity given its high diagnostic yield. Findings of chronic interstitial pneumonitis and focal organizing pneumonia are suggestive of sirolumus-associated lung toxicity in solid organ transplant patients on sirolimus presenting with respiratory symptoms. CLINICAL IMPLICATIONS: Where available, including TBB in the workup for sirolumus-associated lung toxicity is essential in confirming the diagnosis. Development of sirolimus-associated lung toxicity in solid organ transplant patients highlights the need for diagnostic criteria that helps in early diagnosis and management, in order to avoid compromising patients’ allografts long-term survival at the expense of inducing a devastating lung disease that patients and physicians would end up regretting. Pulmonologists need to be more familiar with sirolimus-associated lung toxicity different histological patterns and have a lower threshold for TBB in the appropriate setting. DISCLOSURE: The following authors have nothing to disclose: Zaid Ammari, Faisal Khateeb, Aahd Kubbara, Yousef Abdel-Aziz, Andrew Kobalka, Fadi Safi No Product/Research Disclosure Information

Interstitial lung disease in infancy: an unusual presentation of CD40 ligand deficiency

Introduction: Childhood interstitial lung disease (chILD) syndrome describes findings of respiratory symptoms and diffuse abnormalities on lung imaging. Immunodeficiency and immune dysregulation are increasingly recognized as potential causes of these clinical findings. Patients with CD40 ligand (CD40L) deficiency typically present with sinopulmonary and opportunistic infections secondary to impairments in both humoral and cellular immunity. chILD syndrome has not previously been reported as a presenting feature of this disease.Objectives: We describe a patient with CD40L deficiency, caused by a novel mutation in CD40LG (c.464 T>A, p.Leu155Gln), who presented in infancy with chILD syndrome and lung biopsy findings of chronic interstitial pneumonitis and patchy pulmonary glycogenosis.Methods: A left lingula wedge lung biopsy was fixed with formalin and stained for analysis. Whole blood samples from the patient and parents were sent for whole exome sequencing. Flow cytometry to assess CD40L expression on ac...

Methotrexate Induced Lung Toxicity-A Case Report

Methotrexate (MTX) belongs to a class of antimetabolites. It may cause serious side effects like lung problems, lung infections. Methotrexate-induced lung disease, as well as acute or chronic interstitial pneumonitis, is a potentially risky sore, which can happen intensely whenever, amid treatment and has been accounted for at low doses. The diagnosis of drug-induced pulmonary toxicity is generally settled in light of clinical discoveries. The present report describes a case of methotrexate-induced lung toxicity. Biopsy that had done reported as relapsed lymphoma. Then he got admitted for high dose methotrexate and rituximab followed by folinic acid rescue. He tolerated 2 chemotherapies well, without any major complications. He developed fever, cough with expectoration and breathlessness. In view of persisting high grade fever, associated with cough and breathing difficulty, pulmonology consultation was sought and CT done. In medication-induced lung toxicity, the radiologic patterns seen are exceeding factor and rely upon the kind of unfavorable response the patient is experiencing. One possibility in the clinical setting is methotrexate induced lung changes. Differential diagnosis (DD) is alveolitis due to infection. In view of suspected methotrexate induced lung toxicity, planned to withhold next dose of Methotrexate. He was started on high dose steroids. The patient symptomatically improved, fever subsided, counts improved. Prompt diagnosis is vital in light of the fact that early medication actuated lung harm will regularly relapse with cessation of treatment. It was found that the severity of the methotrexate induced lung toxicity is a probable adverse drug reaction (ADR) with Naranjo score of 7.

Allogeneic Bone Marrow Transplant in Pediatric Patients in Kuwait

To describe outcomes of human leukocyte antigen-matched sibling bone marrow transplantation (BMT) in 12 patients: 9 with ?- thalassemia major (TM) and 1 each with severe aplastic anemia, myelodysplastic syndrome and congenital dyserythropoietic anemia. The median age at transplantation was 9 years and the median follow-up was 24 months. Among the TM patients, 6 were in Pesaro risk class II and 3 in class III. The median neutrophil recovery and platelet recovery were 19 and 25 days, respectively. None of the patients had primary graft failure. At the last follow-up, 11 out of 12 patients were alive, free of disease and living normal quality of life. Most of the patients (75%) had acute GVHD grade I-II, in the skin. None of the patients had grade IV regimen-related toxicity. Six patients developed Gram-negative while two had Gram-positive bacteremia, one had probable lung aspergillosis and four developed febrile neutropenia without identifiable microbiological growth during the aplastic phase. Cytomegalovirus reactivation occurred in five patients. We lost one patient who developed severe acute graft-versus-host disease (GVHD) affecting the skin, gut and liver, who later progressed to severe chronic GVHD and severe interstitial pneumonitis. In conclusion, allogenic BMT is feasible and safe in pediatric patients with hematological disorders in Kuwait.

Pleuroparenchymal fibroelastosis as a late complication of chemotherapy agents

To the Editor: We identified six patients with clinical, radiographic and physiological features typical of pleuroparenchymal fibroelastosis (PPFE). In the six cases, PPFE may have been causally related to prior alkylating drugs used to treat malignacy, namely cyclophosphamide in five of the cases and carmustine (BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea)) in one. Based on an extensive review of the literature, we suspect that similar cases may have already been reported in the past 4 decades but have not been recognised either as PPFE or as drug-induced in nature. In 2004, Frankel et al. [1] described a then-new clinicopathologic entity, which they termed “idiopathic PPFE”. The authors identified five patients who had a clinical presentation suggestive of chronic interstitial pneumonitis that did not fit any previously established category of idiopathic interstitial pneumonia. The patients were characterised by significant pleural involvement in the form of pleural thickening, which was more marked in both upper regions. In all five patients, surgical biopsy demonstrated prominent visceral pleural fibrosis with subpleural fibroelastosis and an abrupt transition between the fibrotic area and the near-normal adjoining lung. There was sparing of the underlying lung parenchyma at some depth from the pleural surface, and sparse fibroblast foci were present at the edge of the fibrotic area. Since that seminal report, several cases and small series have been reported that have demonstrated a strikingly similar clinical, radiological and pathological presentation, also characterised by difficult-to-treat pneumothoraces in a sizable fraction of affected patients. In the updated American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias [2], PPFE is included as a separate but well-defined category of rare entities. Little is known about the aetiology of PPFE and …

Natural history of five children with surfactant protein C mutations and interstitial lung disease

Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.