Individualised treatment of COPD exacerbations using biomarkers.

This review highlights key aspects of treating chronic obstructive pulmonary disease (COPD) exacerbation, focusing on the optimisation of systemic corticosteroid and antibiotic use through personalised treatment using biomarkers. Eosinophil-guided therapy reduces corticosteroid usage which might reduce side effects, while procalcitonin-guided therapy contributes to reduced antibiotic consumption. These approaches, documented through well-conducted randomized controlled trials, suggest the possibility of enhancing COPD exacerbation management, reducing potential side effects, and addressing concerns related to antibiotic resistance.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population.

Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65-1.48), VWF-N: HR 1.56 (95% CI 1.07-2.27), and VWF-A: HR 0.78 (95% CI 0.52-1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.

Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases.

INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.

Persistence and genetic adaptation of Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

OBJECTIVES: It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage. METHODS: Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142). RESULTS: A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated. DISCUSSION: Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.

Adrenal suppression in patients with chronic obstructive pulmonary disease treated with glucocorticoids: Role of specific glucocorticoid receptor polymorphisms.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids, and thus may alter the therapeutic effects of glucocorticoids. We investigated the prevalence of adrenal suppression after treatment with glucocorticoids and evaluated whether GR SNPs were associated with altered risks of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). METHODS: In an observational prospective cohort study, we recruited 78 patients with severe COPD receiving 5 days glucocorticoid treatment for an exacerbation of COPD. In total, 55% of these patients were also receiving regular inhaled corticosteroids (ICS). Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK, and 9ß SNPs. RESULTS: The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ 420 nmol/L) 30 days after glucocorticoid treatment was 4/78 (5%). There was no difference between carriers and non-carriers of the polymorphisms (Bcl1, 9ß, ER22/23K, and N363S) in corticotropin stimulated plasma-cortisol concentrations. In the haplotype analyses, we included the 50 patients who had a high-sensitivity (76%), a low-sensitivity (4%), or a wild-type (20%) GR haplotype. There was no difference in the frequency of adrenal suppression or metabolic disorders between the two stratified groups: (a) high-sensitivity (Bcl1 and/or N363S) haplotypes vs. (b) low-sensitivity (9ß and/or ER22/23K) plus wild-type haplotypes (p > 0.05). Carriers of the high-sensitivity GR gene haplotype exhibited a steeper decline in stimulated P-cortisol with increased ICS dose (slope, -1.35 vs. 0.94; p = 0.17), compared to the group with low-sensitivity or wild-type haplotypes, respectively. CONCLUSIONS: In total, 5% of patients exhibited insufficient adrenal function. The Bcl1 and N363S polymorphisms did not seem to increase the risk of glucocorticoid suppression or metabolic disorders in adults treated with glucocorticoids for COPD exacerbations.

Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease.

BACKGROUND: Inhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD. METHODS: We conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010-2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses. RESULTS: A total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, p<0.0001; high ICS dose: HR 3.58, 95% CI 2.75 to 4.65, p<0.0001; reference: no ICS use). A propensity matched model confirmed the results (high ICS dose compared with no/low/moderate ICS dose: HR 2.05, 95% CI 1.76 to 2.39, p p<0.0001). CONCLUSION: Use of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

[Opioids for refractory dyspnoea in palliation].

Dyspnoea is cardinal symptom in chronic obstructive lung disease and common in palliative phases of cancer and other chronic medical diseases. Low-dose opioids is frequently used off-label. This review examines the evidence and safety as well as administration forms and pharmacokinetics using low dose opioids for dyspnoea. Conclusively, there seems to be clinical efficacy although further studies are needed. Furthermore, the authors recommend Danish Medical Agency to legislate low-dose morphine to palliative patients with refractory dyspnoea.

Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial.

BACKGROUND: Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. METHODS: The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. RESULTS: CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. CONCLUSION: Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02857842 . Submitted August 2nd, 2016.

12-months follow-up of pulmonary tele-rehabilitation versus standard pulmonary rehabilitation: A multicentre randomised clinical trial in patients with severe COPD.

Between March 2016 and October 2017, we randomised 134 patients with severe COPD from 8 hospitals in the Capital Region of Denmark to participate in either standardised, outpatient pulmonary rehabilitation (control group) or on-line, supervised and home-based tele-rehabilitation (intervention group). We found no difference between the groups in the primary outcome: six minutes walking distance (6MWD) after completion of the programme. The current study presents results from the 12-month follow-up with assessment of the 6MWD and analyses of hospitalisation and mortality. There were no significant differences between or within the groups in the 6MWD one year after completion of the programme.

Adherence to early pulmonary rehabilitation after COPD exacerbation and risk of hospital readmission: a secondary analysis of the COPD-EXA-REHAB study.

BACKGROUND: Early pulmonary rehabilitation after exacerbation of chronic obstructive pulmonary disease (COPD) has previously been shown to reduce the risk of hospital admission and improve physical performance and quality of life. However, the impact of attendance at early rehabilitation programmes has not been established. OBJECTIVES: To evaluate the impact of increasing attendance to pulmonary rehabilitation on the risk of hospital admission, physical performance and quality of life in patients attending an early rehabilitation programme after an exacerbation of COPD. METHODS: This study was a secondary exploratory analysis of the randomised controlled trial COPD-EXA-REHAB study, involving patients hospitalised with an exacerbation of COPD. The COPD-EXA-REHAB study compared early pulmonary rehabilitation, starting within 2 weeks after an exacerbation, with standard treatment, that is, the same programme starting 2 months later. The present analysis included only the 70 patients allocated to early pulmonary rehabilitation. RESULTS: At 1-year follow-up, we found an association between the number of sessions attended and a reduction in hospital admissions (incidence rate ratio 0.93 (95% CI 0.88 to 0.99), p=0.02), corresponding to a 7% reduction for each session attended. Similarly, at 2-month follow-up, physical performance was positively associated with sessions attended: the mean Incremental Shuttle Walk Test result improved by 8 m with each session (95% CI 2.54 to 13.56, p=0.005) and the Endurance Shuttle Walk Test result by 44 s (95% CI 18.41 to 68.95, p=0.001). Quality of life, assessed using the COPD Assessment Test, was not significantly associated with the number of attended sessions, with the average score increasing by 0.15 points with each session (95% CI -0.35 to 0.65, p=0.55). CONCLUSION: Increased attendance at early pulmonary rehabilitation after exacerbation of COPD was associated with reduced risk of hospital admission and improved physical performance.

Increased respiratory morbidity in individuals with interstitial lung abnormalities.

BACKGROUND: Interstitial lung abnormalities (ILA) are common in participants of lung cancer screening trials and broad population-based cohorts. They are associated with increased mortality, but less is known about disease specific morbidity and healthcare utilisation in individuals with ILA. METHODS: We included all participants from the screening arm of the Danish Lung Cancer Screening Trial with available baseline CT scan data (n = 1990) in this cohort study. The baseline scan was scored for the presence of ILA and patients were followed for up to 12 years. Data about all hospital admissions, primary healthcare visits and medicine prescriptions were collected from the Danish National Health Registries and used to determine the participants' disease specific morbidity and healthcare utilisation using Cox proportional hazards models. RESULTS: The 332 (16.7%) participants with ILA were more likely to be diagnosed with one of several respiratory diseases, including interstitial lung disease (HR: 4.9, 95% CI: 1.8-13.3, p = 0.008), COPD (HR: 1.7, 95% CI: 1.2-2.3, p = 0.01), pneumonia (HR: 2.0, 95% CI: 1.4-2.7, p <  0.001), lung cancer (HR: 2.7, 95% CI: 1.8-4.0, p <  0.001) and respiratory failure (HR: 1.8, 95% CI: 1.1-3.0, p = 0.03) compared with participants without ILA. These findings were confirmed by increased hospital admission rates with these diagnoses and more frequent prescriptions for inhalation medicine and antibiotics in participants with ILA. CONCLUSIONS: Individuals with ILA are more likely to receive a diagnosis and treatment for several respiratory diseases, including interstitial lung disease, COPD, pneumonia, lung cancer and respiratory failure during long-term follow-up.

Risk factors for diagnostic delay in idiopathic pulmonary fibrosis.

BACKGROUND: Surveys and retrospective studies of patients with idiopathic pulmonary fibrosis (IPF) have shown a significant diagnostic delay. However, the causes and risk factors for this delay are not known. METHODS: Dates at six time points before the IPF diagnosis (onset of symptoms, first contact to a general practitioner, first hospital contact, referral to an interstitial lung disease (ILD) centre, first visit at an ILD centre, and final diagnosis) were recorded in a multicentre cohort of 204 incident IPF patients. Based on these dates, the delay was divided into specific patient-related and healthcare-related delays. Demographic and clinical data were used to determine risk factors for a prolonged delay, using multivariate negative binomial regression analysis. RESULTS: The median diagnostic delay was 2.1 years (IQR: 0.9-5.0), mainly attributable to the patients, general practitioners and community hospitals. Male sex was a risk factor for patient delay (IRR: 3.84, 95% CI: 1.17-11.36, p = 0.006) and old age was a risk factor for healthcare delay (IRR: 1.03, 95% CI: 1.01-1.06, p = 0.004). The total delay was prolonged in previous users of inhalation therapy (IRR: 1.99, 95% CI: 1.40-2.88, p <  0.0001) but not in patients with airway obstruction. Misdiagnosis of respiratory symptoms was reported by 41% of all patients. CONCLUSION: Despite increased awareness of IPF, the diagnostic delay is still 2.1 years. Male sex, older age and treatment attempts for alternative diagnoses are risk factors for a delayed diagnosis of IPF. Efforts to reduce the diagnostic delay should focus on these risk factors. TRIAL REGISTRATION: This study was registered at http://clinicaltrials.gov (NCT02772549) on May 10, 2016.

Danish respiratory society position paper: palliative care in patients with chronic progressive non-malignant lung diseases.

Background:  Chronic non-malignant lung diseases such as chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD) result in reduced quality of life (QoL), a high symptom burden and reduced survival. Patients with chronic non-malignant lung disease often have limited access to palliative care. The symptom burden and the QoL of these patients resembles patients with cancer and the general palliative approach is similar. However, the disease trajectory is often slow and unpredictable, and the palliative effort must be built on accessibility, continuity and professional competences. The Danish Health Authority as well as the WHO recommends that there is access to palliative care for all patients with life-threatening diseases regardless of diagnosis. In 2011, the Danish Health Authority requested that the national medical societies would to formulate guidelines for palliation. Methods: In 2015, a group of members of the Danish Respiratory Society (DRS) was appointed for this purpose. It was composed of experienced ILD and COPD researchers as well as clinicians from different parts of Denmark. A literature review was made, a draft was prepared, and all recommendations were agreed upon unanimously. Results: The Danish version of the position paper was finally submitted for review and accepted by all members of DRS. Conclusion: In this position paper we provide recommendations on the terminology of chronic and terminal lung failure, rehabilitation and palliative care, advanced care planning, informal caregivers and bereavement, symptom management, the imminently dying patient, and organization of palliative care for patients with chronic non-malignant lung diseases.

[Treatment limitations or discontinuation in patients with benign pulmonary diseases].

The decision to limit or discontinue treatment is a difficult issue, which all physicians will face. Timely communication with information on treatment possibilities and limitations, respectful listening to patients' and informal caregivers' wishes and early palliation is recommended in a stable phase. In some situations, it is better to stop life-prolonging treatment and optimise quality of life in patients with benign pulmonary diseases. Decision on treatment limitations or discontinuation is best taken at a conference and should be based on the patient's wishes, the disease stage and progression and potential reversible components.

Interstitial lung abnormalities are associated with increased mortality in smokers.

OBJECTIVE: The aim of this study was to investigate whether smokers with incidental findings of interstitial lung abnormalities have an increased mortality during long-term follow-up, and review the contributing causes of death. METHODS: Baseline CT scans of 1990 participants from the Danish Lung Cancer Screening Trial were qualitatively assessed for predefined interstitial lung abnormalities of any severity. Inclusion criteria for this lung cancer screening trial included current or former smoking, > 20 pack-years, and age 50-70 years. Patients were followed up for up to 12 years. RESULTS: We found interstitial lung abnormalities in 332 participants (16.7%). Interstitial lung abnormalities were associated with increased all-cause mortality in the full cohort (HR: 2.0, 95% CI: 1.4-2.7, P < 0.001) and in lung cancer-free participants (HR: 1.6, 95% CI: 1.1-2.4, P = 0.007). The findings were associated with death from lung cancer (HR: 3.2, 95% CI: 1.7-6.2, P < 0.001) and non-pulmonary malignancies (HR: 2.1, 95% CI: 1.1-4.0, P = 0.02). Participants with fibrotic and non-fibrotic interstitial lung abnormalities had similar survival. CONCLUSION: Interstitial lung abnormalities were common in this lung cancer screening population of relatively healthy smokers and were associated with mortality regardless of the interstitial morphological phenotype. The increased mortality was partly due to an association with lung cancer and non-pulmonary malignancies.

Screening for TB by sputum culture in high-risk groups in Copenhagen, Denmark: a novel and promising approach.

INTRODUCTION: Evidence on screening high-risk groups for TB by mobile X-ray in low-incidence countries is building, but knowledge on other possible screening methods is limited. In this retrospective study we report results from a community based programme screening for TB by spot sputum culture. METHODS: On seven occasions, from September 2012 through June 2014, we offered TB screening to all persons present at 11 locations where socially marginalised people gather in Copenhagen. Spot sputum samples from participants were examined by smear microscopy and culture. Genotype, nucleic acid amplification test and chest X-ray were done if TB was found. RESULTS: Among 1075 participants, we identified 36 cases of TB. Twenty-four cases (66.7%) were identified at the first screening of each participant, that is, the prevalence of TB was 2233/100 000. Thirty-five (97%) of the TB cases were culture-positive and seven (19.4%) were smear-positive. Twelve out of 21 (57.1%) cases tested were nucleic acid amplification test positive. Twenty-eight (77.8%) had chest X-ray suggestive of TB. All patients with TB started treatment, 30 (83.3%) had a successful outcome. DISCUSSION: Screening for TB by spot sputum culture is possible and a promising alternative to mobile X-ray in a community based screening programme. 22.2% did not have chest X-ray suggestive of TB and would not have been identified using mobile X-ray. Most of the TB cases were smear-negative, suggesting that they were identified at an early, less infectious stage, which is essential in order to prevent transmission and gain infection control.

Routine examination for tuberculosis is still indicated during bronchoscopy for pulmonary infiltrates.

INTRODUCTION: Tuberculosis (TB) can present in numerous ways and can be radiological indistinguishable from cancer. In several guidelines for bronchoscopy (FOB) in low-incidence areas, a Mycobacterium tuberculosis test is only recommended when TB is clinically suspected. Due to the expenses associated with M. tuberculosis cultures, we did an analysis of tests obtained by FOB and other invasive procedures (endoscopic ultrasound (EUS)-guided needle biopsy via the oesophagus or trachea and percutaneous needle lung biopsy (PNLB)). METHODS: All patients tested positive for M. tuberculosis by culture and with samples obtained by FOB, EUS or PNLB in the 2008-2012 period were identified retrospectively in two centres in a low-incidence area (Copenhagen, Denmark). Patient records and radiological reports were reviewed. RESULTS: A total of 57 (1.2%) patients out of the 4,680 tested were M. tuberculosis culture positive. Of the 57 patients, 40.3% (n = 23) presented with isolated upper lobe infiltrates and 29.8% (17) with cavitating infiltrates. Isolated chest lymphadenopathy was seen in 8.8% (n = 5). In 33.3% (n = 19) of the patients, radiography was not typical of TB (not upper lobe, no cavity, not isolated lympadenopathy, not miliary). Of the 57 patients, 48 were diagnosed by FOB, six by EUS and three by PNLB. M. tuberculosis samples were taken in an estimated 34% of all procedures. CONCLUSION: M. tuberculosis culturing should always be considered when performing FOB in patients with lung infiltrates of unknown origin, even in a low-incidence country as Denmark. EUS and PNLB should also be considered when sampling material. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Being publicly diagnosed: a grounded theory study of Danish patients with tuberculosis.

INTRODUCTION: Tuberculosis (TB) is a disease which affects people worldwide, but there is knowledge lacking about patients' experiences in low-prevalence and high-income countries. AIM: To provide a theoretical framework for the process of being diagnosed with tuberculosis in a Danish setting. METHOD: A grounded theory design with field studies and qualitative interviews, following the recommendations from Glaser and Strauss. RESULT: A process of being publicly diagnosed was identified, which developed during the patient's trajectory from being on the way to becoming a patient, becoming a patient with TB, and finally being in medical treatment. Before being diagnosed with TB, patients were weighing between biding their time and deciding to undergo an examination. Social pressure and feelings of social responsibility tended to affect the decision. Having undergone the examination(s), the patients were publicly diagnosed. Being publicly diagnosed meant changing social interactions and fighting to regain control. CONCLUSION: Findings offer new insight and an empirically derived basis for developing interventions aimed at reducing the burden of being diagnosed with tuberculosis and increasing the wellbeing of the patients.