Detection of Interstitial Lung Disease in Rheumatoid Arthritis by Thoracic Ultrasound. A Diagnostic Test Accuracy study.

OBJECTIVE: The Objective was to determine the diagnostic accuracy of thoracic ultrasound (TUS) for detecting (ILD) in rheumatoid arthritis (RA) with respiratory symptoms. METHODS: Individuals with RA visiting Rheumatological outpatient clinics in the Region of Southern Denmark were systematically screened for dyspnoea, cough, recurrent pneumonia, prior severe pneumonia or a chest X-ray indicating interstitial abnormalities. Eighty participants with a positive screening were consecutively included. Individuals were not eligible if they had a chest high-resolution CT (HRCT) <12 months or were already diagnosed with ILD. A blinded TUS expert evaluated TUS, and TUS was registered as positive for ILD if ≥10 B-lines or bilateral thickened and fragmented pleura were present. The primary outcomes were TUS's sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). An ILD-specialised thoracic radiologist assessed HRCT, followed by a multi-disciplinary team discussion, which was the reference standard. The accepted window of HRCT was <30 days after TUS was performed. RESULTS: 77 participants received HRCT <30 days after TUS, and 23 (30%) were diagnosed with ILD. TUS had a sensitivity of 82.6% (95% CI: 61.2% to 95.0%) and a specificity of 51.9% (95% CI: 37.8% to 65.7%), corresponding to a PPV of 42.2% (95%CI 27.7% to 57.8%) and an NPV of 87.5% (95% CI 71.0% to 96.5%). CONCLUSION: To our knowledge, this prospective study is the first to use respiratory symptoms in RA as inclusion criteria. Systematic screening for respiratory symptoms combined with TUS can reduce the diagnostic delay of ILD in RA.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.

Humoral antibody response following mRNA vaccines against SARS-CoV-2 in solid organ transplant recipients; a status after a fifth and bivalent vaccine dose.

Background: In solid organ transplant (SOT) recipients, the humoral response following COVID-19 vaccination is reduced, as a result of their immunosuppressed treatment. In this study, we investigated antibody concentrations after booster vaccinations until the fifth dose, the latter by monovalent or bivalent BA1 or BA4/5 vaccines. In addition, we evaluated the efficacy of vaccination by recording breakthrough infections, hospitalizations, and deaths. Method: This prospective cohort study included 438 SOT recipients (>18 years) vaccinated with mRNA vaccines against COVID-19 from January 2021 until March 2023. Blood samples were drawn before and after each vaccination and tested for SARS-CoV-2 spike RBD IgG antibodies with the lowest and highest cut-off at 7.1 and 5,680 BAU/mL, respectively. Vaccine information, breakthrough infections, and hospitalizations were collected from the medical records. Results: Most participants received BNT162b2 and 61.4% received five vaccine doses. The response proportion in SOT recipients increased from 86.7% after the fourth dose to 93.0% following the fifth dose. Antibody concentration decreased with 142.7 BAU/mL between the third and fourth dose (median 132 days, Quartile 1: 123, Quartile 3: 148) and 234.3 BAU/mL between the fourth and fifth (median 250 days, Quartile 1: 241, Quartile 3: 262) dose among those without breakthrough infection (p=0.34). When comparing the Omicron BA.1 or Omicron BA.4/BA.5 adapted vaccines, no significant differences in antibody concentration were found, but 20.0% of SOT recipients receiving a monovalent fifth vaccine dose had a breakthrough infection compared to 4.0% and 7.9% among those who received BA.1 and BA.4/BA.5 adapted vaccines, respectively (p=0.04). Since January 2021, 240 (54.8%) participants had a breakthrough infection, and 22 were hospitalized, but no deaths were observed. Conclusions: The fifth COVID-19 vaccine dose raised antibody response to 93.0% of the study population. Additional booster doses, as well as bivalent vaccines, led to higher levels of antibody concentration in SOT recipients. We found a lower incidence of breakthrough infections among SOT recipients after receiving a bivalent vaccine as a fifth dose compared to those receiving a monovalent dose. Antibody concentrations did not wane when the time between doses was prolonged from four to eight months.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Diseases and Peripheral Pulmonary Lesions - A Stepwise Approach.

Transbronchial lung cryobiopsy (TBLC) is an invasive procedure increasingly implemented during the last decade as an alternative to video-assisted thoracic surgery lung biopsy (SLB) for diagnosing interstitial lung diseases (ILDs). The indication for TBLC has primarily been to sub-classify a specific ILD subtype when this cannot be achieved on the basis of a preceding multidisciplinary team discussion. Although SLB is considered the gold standard for establishing a histological diagnosis, TBLC has been gradually suggested as the first-choice histological diagnostic modality in patients with unclassified ILDs due to a comparable diagnostic yield with SLB, but superior to SLB in terms of complications, including mortality. During recent years, radial endobronchial ultrasound (R-EBUS) and electromagnetic navigation bronchoscopy (ENB)-guided TBLC for peripheral pulmonary lesions have also been described as safe procedures, which may improve the diagnostic yield compared to forceps biopsies. Still, the diagnostic properties of TBLC rely on the quality of the procedure's performance. This article aims to describe the stepwise approach to conducting TBLC with a flexible bronchoscope for the different indications mentioned, which might be helpful for novice bronchoscopists performing TBLC.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

EQUAL CPA Score 2022: a tool to measure guideline adherence for chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) can complicate underlying pulmonary diseases, and clinical management of CPA is challenging. Guidelines support clinicians but due to the complexity of the disease they can be difficult to adhere to. OBJECTIVES: To map current guideline recommendations for the clinical management of CPA into a scoring tool to facilitate and quantify guideline adherence in clinical practice. METHODS: Recommendations for diagnosis, treatment and follow-up of CPA presented in the current ESCMID/ERS/ECMM and CPAnet guidance documents were assembled and weighed on the basis of their strength of recommendation and level of evidence. RESULTS: Twenty-seven recommendations were identified, resulting in a total maximum EQUAL CPA Score of 51. For diagnostics (ScoreMax = 27), a strong emphasis on expert consultation, culture, direct microscopy, histopathology, serology and imaging was reflected in respective points, whereas molecular techniques and susceptibility testing count into the diagnostics score to a lesser extent.Ten treatment recommendations (ScoreMax = 14), including antifungal therapy, therapeutic drug monitoring and treatment duration, were identified. Surgery, where indicated, adds three points. For refractory disease or intolerance of first-line antifungal treatment, optimal second-line treatment added another two points.During follow-up (ScoreMax = 10), response assessment via imaging gave three points, while culture and serology added two points each to the ScoreMax. CONCLUSION: The EQUAL CPA Score intents to be used as a comprehensive tool for measuring guideline adherence. If adherence to current guidelines is associated with clinical outcome, this will be assessed in future studies.

Incidence, prevalence and regional distribution of systemic sclerosis and related interstitial lung Disease: A nationwide retrospective cohort study.

OBJECTIVE: To investigate incidence and prevalence of Systemic Sclerosis (SSc) and association with interstitial lung disease (SSc-ILD) in a nationwide population-based study. METHODS: Patients with an incident diagnosis of SSc in 2000-2016 were identified in the Danish National Patient Registry and categorised based on diagnosis of ILD. Incidence- and prevalence proportions were calculated based on the annual population estimates. A cox proportional hazards model was used to evaluate the association between age, sex, region and marital status and presence of ILD. RESULTS: In total, 1869 patients with SSc were identified; 275 patients (14.7%) had SSc-ILD. The majority of patients were females (75.5%). The percentage of males was higher in SSc-ILD than in SSc alone (30.9% and 23.4%, p = 0.008). Median time from SSc to ILD diagnosis was 1.4 years (range 0-14.2). ILD was diagnosed from ≤4 years before to ≥7 years after SSc. Development of ILD was associated with male gender (HR 1.75, 95% CI 1.15-2.66), age 41-50 (HR 1.81, 95% CI 1.07-3.05) and residency in the North Denmark Region (HR 1.95, 9 5% CI 1.12-3.40). Mean annual incidence proportion of SSc was 2.9/100,000 and mean annual prevalence proportion was 16.8/100,000. The incidence remained stable, but prevalence proportion increased from 14.1 - 16.5/100,000 in 2000-2008 to 17.9-19.2/100,000 in 2009-2016. CONCLUSION: The prevalence of SSc increased during the study period, while the incidence remained stable. The prevalence of SSc-ILD was 14.7% and thus less frequent than expected. Male sex and age between 41 and 50 years were associated with ILD.

SARS-CoV-2 antibody kinetics in blood donors with a previously positive SARS-CoV-2 antibody test within a seroprevalence survey.

The persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a matter of importance regarding the coronavirus disease 19 (COVID-19) pandemic. To observe antibody dynamics, 105 blood donors, positive for SARS-CoV-2 antibodies by a lateral flow test within a seroprevalence study, were included in this study. Thirty-nine (37%) of 105 the donors were confirmed positive by a total Ig Wantai enzyme-linked immunosorbent assay (ELISA). Three (8%) in this group of 39 reported severe and 26/39 (67%) mild to moderate COVID-19 symptoms. By further ELISA-testing, 33/39 (85%) donors were initially positive for IgG antibodies, 31/39 (79%) for IgA, and 32/39 (82%) for IgM, while 27/39 (69%) were positive for all three isotypes. Persistence of IgG, IgA, and IgM was observed in 73%, 79%, and 32% of donors, respectively, after 6-9 months of observation. For IgM antibodies, the decline in the proportion of positive donors was statistically significant (p = 0.002) during 12 months observation, for IgG only the decline at 3 months was statistically significant (p = 0.042). Four donors exhibited notable increases in antibody levels. In conclusion, persistent SARS-CoV-2 IgA antibodies and IgG antibodies at 6-9 months are present in approximately three of four individuals with previous mild to moderate COVID-19.

Granulomatous-lymphocytic interstitial lung disease: an international research prioritisation.

The first ever research prioritisation exercise in GLILD: this survey identified areas of interest in the diagnosis, treatment and management of GLILD, which can be used as a roadmap for future research https://bit.ly/3nVuzti.

Lung ultrasound assessment for pneumothorax following transbronchial lung cryobiopsy.

BACKGROUND: Iatrogenic pneumothorax is a common and clinically important transbronchial cryobiopsy (TBCB) complication. A study was conducted to assess the diagnostic accuracy and clinical impact of immediate post-procedure lung ultrasound for diagnosing iatrogenic pneumothorax in patients suspected of interstitial lung disease (ILD) undergoing TBCB. STUDY DESIGN AND METHODS: In patients undergoing TBCB due to suspected ILD, lung ultrasound of the anterior surface of the chest was performed immediately after the TBCB procedure prior to extubation. Presence of lung point was used as a definite sign of pneumothorax. Chest radiography was routinely performed 2 h after TBCB and was used as the reference standard. RESULTS: A total of 141 consecutive patients were included. Post-procedure lung ultrasound identified definite pneumothorax in five patients (3.6%, 95% confidence interval (CI) 1.5-8.3%). Chest radiography at 2 h identified 19 patients (13.5%, 95% CI 8.7-20.2%) with pneumothorax following TBCB. The diagnostic accuracy of lung ultrasound for diagnosing pneumothorax was as follows: sensitivity: 21.1% (95% CI 6.1-45.6%), specificity: 99.2% (95% CI 95.5-100.0%), positive predictive value (PPV): 80.0% (95% CI 28.4-99.5%) and negative predictive value (NPV): 89.0% (95% CI 82.5-93.7%). Post-procedure lung ultrasound had a clinical impact in five patients (3.6%, 95% CI 1.5-8.3), of which four had a pleural drain inserted prior to extubation and one underwent prolonged observation prior to extubation. INTERPRETATION: Lung ultrasound performed immediately following TBCB has a clinical impact by identifying patients with pneumothorax in need of immediate treatment prior to extubation and by monitoring pneumothorax size in the operating room. Supplementary imaging prior to patient discharge is still needed however, as the majority of pneumothoraxes develop later in the post-procedure period.

Ultrasound-guided Lung Biopsy in the Hands of Respiratory Physicians: Diagnostic Yield and Complications in 215 Consecutive Patients in 3 Centers.

BACKGROUND: The aim of the study was to determine the diagnostic yield and prevalence of complications of ultrasound-guided transthoracic needle aspiration biopsies (US-TTNAB) performed by respiratory physicians after implementation of the procedure in an everyday clinical setting at 3 different centers. METHODS: Patients were included if they during the period from January 2012 to August 2014 had a registered US-TTNAB procedure code or if a US biopsy registration form had been filled out at either of the participating centers. Histology or cytology results were used as a reference test for diagnoses that could be made based on these results. Reference test for the remaining diagnoses was clinical follow-up. The diagnostic yield of US-TTNAB was defined as the proportion of patients in which the result of the US-TTNAB was consistent with the reference test. RESULTS: A total of 215 patients in which a primary US-TTNAB had been performed were identified. The most common biopsy sites were lungs and pleurae with a total of 164 (76.3%) patients and 31 patients (14.4%), respectively. US-TTNAB diagnostic yield was 76.9% (95% CI, 70.3%-83.4%) for malignant diagnoses and 47.6% (95% CI, 31.9%-63.4%) for nonmalignant diagnoses. The most common complications of US-TTNAB were pneumothorax (2.5%; 95% CI, 0.03%-4.6%) and pain at the biopsy site (2%; 95% CI, 0.04%-3.9%). No fatalities related to US-TTNAB were observed. CONCLUSION: US-TTNAB performed by respiratory physicians is a safe procedure with a low risk of complications and the diagnostic yield to establish a malignant diagnosis is acceptable.