A new definition and treatment options of allergic alveolitis.

In this review, we discuss a new definition and treatment options of allergic alveolitis (AA). AA is an immune-mediated interstitial lung disease triggered by inhaled antigens, it is defined as non-fibrotic (inflammatory) and/or fibrotic, and diagnosis relies on a multidisciplinary approach using clinical, radiological and sometimes histological assessments. Treatment involves early antigen elimination and may include corticosteroids or other immunosuppressants. Prognosis varies from reversible inflammation to irreversible fibrosis. Early detection is crucial for better outcomes.

Lifestyle and demographic associations with 47 inflammatory and vascular stress biomarkers in 9876 blood donors.

BACKGROUND: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences. METHODS: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking. RESULTS: Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers. CONCLUSION: This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools.

Blood-based biomarkers are circulating molecules that can help to indicate health or disease. Biomarker levels may vary depending on demographic and lifestyle factors such as age, sex, smoking status, and body mass index. Here, we examine the effects of these demographic and lifestyle factors on levels of biomarkers related to activation of the immune system and cardiovascular stress. Measurements of 47 different proteins were performed on blood samples from nearly 10,000 healthy Danish blood donors. Measurement data were linked with questionnaire data to assess effects of lifestyle. We found that immune activation and vascular stress generally increased with age, BMI, and smoking. As these measurements are from healthy blood donors they can serve as a reference for expectable effects and inflammation levels in healthy individuals. Knowledge about the healthy state is important for understanding disease progression and optimizing care.

Substantial decrease of PFAS with anion exchange resin treatment - A clinical cross-over trial.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are heat and stain resisting chemicals. They are persistent, bioaccumulating and spread ubiquitously. Many hotspots where humans are exposed to high levels of PFAS have been reported. A few small observational studies in humans suggest that treatment with an Anion Exchange Resin (AER) decreases serum PFAS. This first clinical controlled crossover study aimed to assess whether AER decreases perfluorooctanesulfonic acid (PFOS) in highly exposed adults. METHODS: An open label 1:1 randomized treatment sequence crossover study with allocation to oral AER (cholestyramine 4 g three times daily) or observation for 12 weeks was conducted among citizens from a PFAS hotspot. Main inclusion criteria was serum PFOS > 21 ng/mL. Primary endpoint was change in serum PFOS levels between treatment and observational period. RESULTS: In total, 45 participants were included with a mean age of 50 years (SD 13). Serum PFOS baseline median was 191 ng/mL (IQR: 129-229) and decreased with a mean of 115 ng/mL (95 % CI: 89-140) on treatment, and 4.3 ng/mL in observation period corresponding to a decrease of 60 % (95 % CI: 53-67; p < 0.0001). PFHxS, PFOA, PFNA and PFDA decreased during treatment between 15 and 44 %. No serious adverse events were reported. CONCLUSIONS: Oral treatment with AER significantly lowered serum PFOS concentrations suggesting a possible treatment for enhancing elimination of PFOS in highly exposed adults.

A rare case of sarcoid myelitis complicating Löfgren's syndrome.

Neurosarcoidosis is a rare and serious condition. Rapid diagnosis and treatment are crucial to prevent morbidity and mortality. When neurological symptoms are not present at the time of diagnosis, CNS involvement can be undetected. We present a case of neurosarcoidosis complicating Löfgren's syndrome and discus the challenges in diagnostics and treatment, that can be encountered.

Health perspectives and handling of PFAS contamination in Denmark.

Per- and polyfluorinated alkyl substances (PFAS) are a group of man-made extremely persistent chemicals that have been spread worldwide since the 1950s due to their properties as effective water- and grease-repellent and heat- and temperature-resistant. They are associated with an increasing number of health effects including immune and hormonal disturbances and some types of cancer. We present a review of PFAS pollution in Denmark, the current human exposure, suspected health effects, and patient management in environmental medicine.

Fatigue in Patients with Sarcoidosis in Denmark.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease of unknown etiology, primarily affecting the lungs and thoracic lymph nodes. Fatigue is a frequent and disabling symptom in sarcoidosis with a significant impact on quality of life. In Denmark, the incidence of sarcoidosis has increased; however, the extent and risk factors of fatigue have not been investigated and no recent reports of the characteristics of patients with sarcoidosis in Denmark exist. AIM: To assess the frequency of fatigue in patients with sarcoidosis in Denmark at diagnosis and to investigate if fatigue correlated with relevant disease parameters. Moreover, to characterize patients with sarcoidosis in Denmark at time of diagnosis. METHODS: Data were collected in 150 patients with recently diagnosed sarcoidosis. Fatigue was measured using the Fatigue Assessment Scale (FAS). Patients with fatigue were compared to non-fatigue patients regarding clinical parameters. RESULTS: FAS was completed by 145 of 150 patients. Fifty-one percent reported significant fatigue. Mean FAS score was 23.6 and 51% had a FAS score ≥ 22. Fatigue in 89 incident patients did not correlate significantly with demographics, physiological, or clinical parameters. Fifty-nine percent were males. Mean age was 47 years; mean values (% predicted) for pulmonary function tests were normal and 71% at Scadding stage 0-I. CONCLUSION: In Denmark, fatigue was frequent in patients with sarcoidosis. The majority of patients had mild disease at diagnosis and were older but lower at Scadding stage at diagnosis compared to previous cohorts.

Current best clinical practices for monitoring of interstitial lung disease.

INTRODUCTION: Interstitial lung diseases (ILDs) are a heterogeneous group of inflammatory and/or fibrotic conditions with variable outcome and often a dismal prognosis. Since many ILDs are progressive in nature, monitoring of signs and symptoms of progression is essential to inform treatment decisions and patient counseling. Monitoring of ILDs is a multimodality process and includes all aspects of the disease, e.g. measurement of pulmonary function and exercise capacity, symptom registration and quality of life (QoL), imaging, comorbidities and/or involvement of other organs to assess disease activity, symptom burden, treatment effects, adverse events, the need for supportive and palliative care, and lung transplantation. AREAS COVERED: For this narrative review, we searched the PUBMED database to identify articles relevant for monitoring ILDs, including pulmonary function tests, exercise capacity, imaging, telemedicine, symptoms, and QoL. EXPERT OPINION: Due to the high heterogeneity of the ILDs and their disease course, an individualized multimodality approach must be applied. Future strategies include use of telemedicine for home monitoring of lung function and symptoms, use of artificial intelligence to support automatized guidance of patients, computerized evaluation of ILD changes on imaging, and new imaging tools with less radiation dosage.

[Antifibrotic therapy in other fibrotic interstitial lung diseases than idiopathic pulmonary fibrosis].

Numerous studies have shown that perioperative heparin bridging in patients treated with a vitamin K antagonist leads to an increased incidence of bleeding and so far, there is no evidence that it leads to a significant reduction in postoperative thromboembolism as summarised in this review. Prophylactic dosage of heparin is recommended after major surgery. Heparin bridging is not relevant in patients receiving a direct oral anticoagulant due to the rapid onset and offset of action of DOACs.

International multidisciplinary team discussions on the diagnosis of idiopathic non-specific interstitial pneumonia and the development of connective tissue disease.

BACKGROUND: Idiopathic Non-Specific Interstitial Pneumonia (iNSIP) is a rare interstitial lung disease, diagnosed, by definition, on the basis of a multidisciplinary team discussion (MDD). Association with an autoimmune background has been suggested in iNSIP. AIMS: To test the feasibility of conducting a multinational MDD to review the diagnosis in iNSIP cases and to estimate the emergence of connective tissue disease (CTD) during follow-up. METHODS: Investigators from three expert centers (Denmark, Estonia and Norway) met and discussed cases of biopsy-proven iNSIP at an international MDD. The cases were previously diagnosed at a national level between 2004 and 2014. Based on clinical, radiographic and pathological data, the diagnosis of iNSIP was re-evaluated and a consensus diagnosis was made. Cases incompatible with iNSIP were excluded. Relevant data were registered comprising any development of CTD. RESULTS: In total, 31 cases were discussed and 23 patients were included with a diagnosis of iNSIP. The mean follow-up time was 57 months. None of the patients developed CTD according to the rheumatologic criteria during the follow up period. Four patients (17.4%) met the criteria for interstitial pneumonia with autoimmune features. CONCLUSION: We found that an international MDD was a feasible and valuable tool in the retrospective diagnostic evaluation of iNSIP. Diagnosis was changed in a statistically significant number of patients by our international MDD team. None of the patients developed CTD during follow-up.

Changes in management of idiopathic pulmonary fibrosis: impact on disease severity and mortality.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease (ILD) with a median survival of 3-5 years. The aim of the present study was to evaluate disease severity and survival in patients diagnosed with IPF in the era of antifibrotic therapies compared with an earlier IPF cohort. METHODS: We identified all patients with fibrotic ILD in the hospital electronic case record system between 2011 and 2016, and reviewed each case in order to identify incident patients with IPF. We used the GAP-index to compare disease severity and mortality to previous findings in patients with IPF diagnosed at our center between 2003 and 2009. RESULTS: 260 patients were diagnosed with IPF between 2011 and 2016. Mean age was 72.6 years, 79% were male, mean forced vital capacity (FVC) was 80%, and mean diffusing capacity for carbon monoxide (DLco) was 44%. Age, FVC and DLco were significant predictors of mortality, but the presence of a typical usual interstitial pneumonia pattern on HRCT was not. Eighty percent of patients in GAP stage I received antifibrotic therapy, 73% in GAP stage II, and 29% in GAP stage III.The median survival was four years in the 2011-2016 cohort compared with three years in the 2003-2009 cohort. The distribution of patients between GAP stages was unchanged in 2011-2016 compared with 2003-2009, (stage I 34% vs. 32%, stage II 49% vs. 48% and stage III 20% vs. 16%). One-year mortality was 13% in 2011-2016 and 26% in 2003-2009. In severe disease (GAP stage III), one-year mortality was 26% and 54%, respectively, (p=0.019). CONCLUSION: Short-term mortality was significantly lower in the 2011-2016 cohort compared with 2003-2009. This improvement may be linked to changes in treatment strategies towards limited use of corticosteroids. Although early diagnosis of IPF still needs increased focus, the improvement is encouraging.

[Occupational allergic asthma in a laboratory animal keeper with COPD].

This is a case report of a 63-year-old woman, who had worked as a laboratory animal keeper for 23 years. She developed increasing symptoms of rhinitis, coughing and shortness of breath and was diagnosed and treated for COPD based on her smoking history and spirometry results. She went on sick leave due to dyspnoea, and after testing she was diagnosed with occupational allergic asthma from rodents. Her lung function was at this point significantly reduced. Occupational asthma is common, and occupational causes of respiratory symptoms should always be taken into consideration when assessing patients in the working population.

Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians.

Interstitial lung disease (ILD) is a serious complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Other respiratory complications, such as chronic obstructive pulmonary disease and bronchiectasis, are frequent in RA. Infections and drug toxicity are important differential diagnoses and should be considered in the diagnostic work-up of patients with RA presenting with respiratory symptoms. This review provides an overview of the epidemiology and pathogenesis of RA-ILD, the radiological and histopathological characteristics of the disease as well as the current and future treatment options. Currently, there is no available evidence-based therapy for RA-ILD, and immunosuppressants are the mainstay of therapy. Ongoing studies are exploring the role of antifibrotic therapy in patients with progressive fibrotic ILD, which may lead to a new treatment approach for subgroups of patients with RA-ILD.

[Sarcoidosis].

Sarcoidosis is a multisystem granulomatous disease of unknown cause, histologically characterised by non-caseating granulomas. Sarcoidosis most commonly affects the lungs, but all organs can be involved, and there is a variable natural course from an asymptomatic state to a progressive disease. Sarcoidosis is a diagnosis of exclusion, and CT scan, endobronchial ultrasound-guided trans-bronchial needle aspiration and fluorodeoxyglucose positron emission tomography facilitate the diagnostic workup. Patients with severe symptoms or threatening organ damage require systemic treatment.

[Idiopathic pulmonary fibrosis is an overlooked disease].

Idiopathic pulmonary fibrosis is a chronic, progressive and fatal disease which primarily occurs in male patients over 60 years with a smoking history. Cryobiopsy is a new promising method for obtaining lung tissue for histologic analysis with fewer complications than surgical lung biopsy. Cryobiopsy allows more patients to be diagnosed. Antifibrotic treatment has shown to decrease progression and prolong survival time in both early and later stages of the disease. Early diagnosis and treatment are therefore of great importance to prevent disease progression and reduce mortality.

Hypersensitivity pneumonitis among wind musicians - an overlooked disease?

Hypersensitivity pneumonitis (HP) is a complex pulmonary disorder mediated by the immune system and caused by various inhaled antigens against which the subject has previously been sensitized. In about 50% of the cases, the antigen is not identified. Identification and removal of the eliciting antigen is important for the prognosis. We report two cases of HP caused by molds and atypical mycobacteria isolated from wind instruments. We present the first case of HP caused by bassoon playing and another case of HP caused by molds in a trombone. HP caused by fungi and bacteria in wind instruments may be much more common than previously thought. HP caused by fungi and bacteria in wind instruments is probably underdiagnosed; this calls for more clinical attention when HP is suspected.

Airway foreign body aspiration: common, yet easily overlooked! Two interesting cases.

Two cases: A 66-year-old woman was referred to the hospital due to dyspnoea and cough. Seven months prior to referral, the patient had choked on a chunk of nut and grain-filled bread. She had daily cough and dyspnoea. The patient was convinced of an airway foreign body and she contacted her general practitioner and the emergency service several times; they all found this unlikely. Fibre optic bronchoscopy revealed two obstructing nut-like foreign bodies in the right upper and lower lobe, respectively. A 77-year-old man with sarcoidosis developed increased dyspnoea and sputum production. Three weeks earlier, the patient had choked on a magnesium tablet. Everyone was convinced that the tablet had dissolved. Infection was suspected. Chest CT scan was performed showing no obvious signs of infection or progression in sarcoidosis. After the CT scan, the patient coughed up the remains of the tablet and his symptoms resolved. Retrospective evaluation of the CT scan revealed the tablet.

The majority of sick children receive paracetamol during the winter.

INTRODUCTION: Even though fever is a common symptom in childhood, it often worries parents and they may try to reduce discomfort by giving the child paracetamol, which is currently the most commonly sold over-the-counter medicine. The objective of this study was to investigate parent-administered paracetamol in toddlers during a winter-period in relation to symptoms, doctor contacts and severity-rated illness. MATERIAL AND METHODS: The study was conducted as a prospective diary study covering a three-month winter-period. It comprised a cohort of 183 infants born in February 2001 in a district of the capital area in Denmark. RESULTS: According to the parents, a total of 119 toddlers (65%) received paracetamol at least once during the study period; 9.3% of the toddlers received paracetamol for more than ten days. The administration of paracetamol rose as the number of symptoms increased. Paracetamol was given in 37% of days with fever. The most frequent combinations of symptoms to trigger paracetamol administration were fever and earache with a probability of 64%. For the symptoms of vomiting and earache, the probability was 60%. In the rare cases with monosymptomatic fever, some 23% used paracetamol. CONCLUSION: The majority of ill toddlers received paracetamol if they had several symptoms. However, paracetamol was administrated in 37% of days with fever. This use of paracetamol seems reasonable as the parents differentiate between degrees of illness and withhold paracetamol until the second day of the illness episode.