Genetic variations in idiopathic pulmonary fibrosis and patient response to pirfenidone.

Background: Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles. Methods: Retrospective clinical data were collected from 56 IPF patients and had blood drawn for DNA extraction between 7/2013 and 3/2016, with the last patient followed until 10/2018. Nine SNPs were selected for pharmacogenetic investigation based on prior associations with IPF treatment outcomes or implications for pirfenidone metabolism. Genetic variants were examined in relation to clinical data and treatment outcomes. Results: Of the 56 patients, 38 were males (67.85%). The average age of IPF at diagnosis was 66.88 years. At the initiation of pirfenidone, the average percent predicted FVC was 70.7%, and the average DLCO percent predicted was 50.02% (IQR 40-61%). Among the genetic variants tested, the TOLLIP rs5743890 risk allele was significantly associated with improved survival, with increasing pirfenidone duration. This finding was observed with CC or CT genotype carriers but not for those with the TT genotype (p = 0.0457). Similarly, the TGF-B1 rs1800470 risk allele was also significantly associated with improved survival with longer pirfenidone therapy (p = 0.0395), even though it was associated with disease progression. Conclusion: This pilot study suggests that in IPF patients, the TOLLIP rs5743890 genotypes CC and CT, as well as TGF-B1 rs 1800470 may be associated with increased survival when treated with pirfenidone.

Subclinical high-resolution chest CT scan features in psoriasis.

BACKGROUND: Although psoriasis is considered a systemic disease, no clear association has been established between psoriasis and lung diseases. This study aims to detect and describe subclinical pulmonary involvement in psoriasis patients with various degrees of cutaneous manifestations. METHODS: Adult psoriasis patients with no known active pulmonary disease or respiratory symptoms were screened for subclinical pulmonary manifestations and possible parenchymal changes using high-resolution computed tomography (HRCT) scan of the chest. Patients were classified according to the severity of skin manifestations. The clinical characteristics and radiographic findings of these patients were evaluated. RESULTS: Fifty-nine patients with psoriasis were included, among which 47 (79.7%) had abnormal HRCT scan features. Micronodules were the most common detected lung lesions (66.1%), followed by nonspecific interstitial changes (32.2%), including pleuro-parenchymal band/atelectasis, scarring, and focal ground-glass opacities. Other HRCT findings included emphysematous changes and calcified granulomas. Abnormal HRCT findings correlated with older age and duration of psoriasis but not with the severity of skin manifestations. CONCLUSIONS: Micronodules and minor focal nonspecific interstitial changes were the most detected lung alterations in patients with psoriasis. These findings of the pilot study highlight a possible pulmonary involvement in patients with psoriasis. Larger multicenter studies are needed to clarify these findings further. LIMITATIONS: A major limitation of the study, is the lack of a control group with similar radiologic findings of different conditions done in the same geographical region.

Histoplasma capsulatum Complement Fixation and Immunodiffusion Assay Sensitivity in Culture-Confirmed Cases of Histoplasmosis: a 10-Year Retrospective Review (2011 to 2020).

The detection of antibodies against Histoplasma capsulatum remains a frequently relied-on approach to diagnose histoplasmosis. We retrospectively assessed the performances of complement fixation (CF) and immunodiffusion (ID) assays for anti-Histoplasma antibody detection in patients with culture-confirmed histoplasmosis at Mayo Clinic (Rochester, MN) over a 10-year period (2011 to 2020). Among 67 culture-confirmed patients who also had H. capsulatum CF/ID testing ordered, 51 (67.1%) were immunocompromised, 34 (50.7%) had localized disease, and 51 (76.1%) presented with <3 months of symptoms before testing. H. capsulatum CF and/or ID testing was positive in 47 (70.1%) patients, with both assays being positive in 39 cases. CF was positive in 44 (65.7%) patients, with reactivity against both H. capsulatum mycelial and yeast antigens in 30 (68.2%) cases, whereas 11 (25%) and 3 (6.8%) individuals had antibodies to the CF yeast or mycelial antigen only, respectively. H. capsulatum ID was positive in 42 (62.7%) patients, with the presence of the M-band only or the H- and M-bands in 27 (64.3%) and 15 (35.7%) cases, respectively. Among 18 serially tested patients, 12 remained ID and/or CF positive at the final time point (median, 154 days; range, 20 to 480 days). Serial CF testing showed that antibodies to the mycelial antigen serorevert to negative more frequently (6/11) than antibodies to the yeast antigen (2/13). There was no statistically significant difference in antibody positivity relative to patient immune status, degree of disease dissemination, or symptom duration. Serologic testing remains a valuable asset to support the diagnosis of histoplasmosis, particularly when direct detection methods fail to identify an infection.

Excipient lung disease secondary to intravenous heroin use.

We present a case of a woman who had progressive shortness of breath and wheezing with a mild restrictive pulmonary function pattern. She was initially diagnosed with eosinophilic granulomatosis with polyangiitis on the basis of peripheral eosinophilia, bronchoalveolar lavage eosinophilia (47%) and surgical lung biopsy findings. Six months following her diagnosis, the patient returned because of persistent symptoms, and a second review of the lung biopsy revealed thrombotic lesions in the pulmonary vessels with polarisable foreign body materials, associated giant cell reactions and numerous eosinophil infiltrates, consistent with intravenous drug abuse. Further investigation showed that she had a history of intravenous heroin overdose, and the diagnosis of excipient lung disease was made. This case highlights the importance of expert pathological, radiological and clinical review of complex presentations and the need for a thorough medication and drug use history review.

Association of COVID-19 antigenicity with the development of antineutrophilic cytoplasmic antibody vasculitis.

Inflammatory processes, such as an infection or drug reaction, can cause antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Although quite rare, AAV may occur with SARS-coronavirus disease 2019 (COVID-19) antigenic exposure, either from infection or immunization. We present two cases of AAV: one that developed after COVID-19 infection presenting as diffuse alveolar haemorrhage and another that developed shortly after vaccination, presenting as granulomatous pulmonary nodules. Both patients improved with supportive care and immunosuppressive therapies. This adverse event appears to be a very rare complication of COVID-19 infection or vaccination. Early diagnosis of AAV is important because immunosuppressive therapy may improve patient outcomes.

Improvement of constrictive bronchiolitis (bronchiolitis obliterans) after rituximab therapy in 2 patients with primary sjögren syndrome.

Constrictive bronchiolitis is one of the manifestations of small-airway involvement in primary Sjögren syndrome (SS) and is associated with fixed airflow obstruction despite treatment with bronchodilators, macrolides, corticosteroids, and corticosteroid-sparing agents. Reports have shown a beneficial effect of rituximab on interstitial lung disease associated with SS, but the effect of rituximab on constrictive bronchiolitis is unknown. Herein, we present 2 cases of patients with constrictive bronchiolitis associated with SS who experienced symptomatic improvement and stabilization of pulmonary function testing (PFT) after rituximab therapy. Lung function declined in one of the patients when B cells reconstituted, with improved PFT results on re-administration of rituximab. Our case reports suggest that B cells may be involved in the pathogenesis of SS-associated constrictive bronchiolitis. Therapy targeting B cells may therefore be helpful in treating this debilitating and refractory condition. Further research is warranted.

Diffuse alveolar haemorrhage secondary to haemophilus influenzae in a vaping patient.

Diffuse alveolar haemorrhage (DAH) is known to occur from several infectious and non-infectious aetiologies. Among the infectious aetiologies, Haemophilus influenzae, an organism known to cause community-acquired pneumonia, has not been reported in association with DAH prior to this case. On the other hand, vaping, an evolving epidemic concern, has been linked to various types of lung injury, including DAH. However, DAH related to vaping is only limited to several case reports. Our case describes H. influenzae pneumonia with DAH in a patient known to have vaped until the night prior to elective lobectomy for lung cancer and developed DAH within 24 hours of hospitalisation. He subsequently recovered with treatment. DAH requires immediate recognition, and healthcare providers need to be aware that neither haemoptysis nor decrease in haemoglobin level is necessarily associated. Prior to diagnosis, empirical treatment with intravenous steroids and antibiotics can be life-saving.

Patient-reported quality of life in fibrotic interstitial lung disease: novel assessments of self-management ability and affect.

Patient-reported outcomes in fibrotic interstitial lung disease may be additionally predicted by novel assessments of self-management ability and affect https://bit.ly/3iwP5M2.

Case-control study investigating parameters affecting ventilator-associated events in mechanically ventilated patients.

We analyzed a set of clinical parameters using Cox proportional hazard regressions to yield significant factors associated with the development of ventilator-associated events. In our study, intubation site, certain comorbidities, morphine, prednisone, and nutrition emerged as factors. Additionally, we presented potential mechanisms that require further research to validate.

Primary Amyloidosis of Celiac/Para-Pancreatic Lymph Nodes Diagnosed by Endosonography-Guided Fine Needle Aspiration: A Case Report.

Introduction. Primary amyloidosis is a disorder resulting from the deposition of fibrillary protein in extracellular tissue. Diagnosis of primary amyloidosis in the celiac/para-pancreatic lymph nodes via endoscopic ultrasound-guided fine needle aspiration has not been reported in the literature. In this article, we report our first observation. Our patient is a 64-year-old Caucasian man who was referred to our institution from an outlying hospital for recurrent abdominal pain. Radiological imaging revealed an enlarged abdominal lymph node that was already biopsied under computed tomography needle guidance but diagnosis was not achieved on pathological examination. At our institution, endoscopic ultrasound-guided fine needle aspiration showed enlarged para-celiac/pancreatic lymph nodes. Endosonography-guided fine needle aspiration revealed the diagnosis of primary amyloidosis. The patient tolerated the procedure well with follow-up as an outpatient. Conclusions. Lymph node involvement in amyloidosis is not uncommon. However, the involvement of the pancreatic/celiac lymph nodes by amyloidosis is obscure in this case. This case shows a rare presentation of amyloidosis diagnosed for the first time by the technique of endosonography-guided fine needle aspiration. In the future, this might serve as an establishment to standardize diagnosing abdominal lymph node amyloidosis, once suspected, by endosonography-guided fine needle aspiration.