Incidental pulmonary nodules may lead to a high proportion of early-stage lung cancer: but it requires more than a high CT volume to achieve this.

Background: The management of pulmonary nodules plays a critical role in early detection of lung cancer. Computed tomography (CT) has led to a stage-shift towards early-stage lung cancer, but regional differences in survival rates have been reported in Denmark. This study aimed to evaluate whether variations in nodule management among Danish health regions contributed to these differences. Material and Methods: The Danish Health Data Authority and Danish Lung Cancer Registry provided data on CT usage and lung cancer stage distribution, respectively. Auditing of lung cancer stage IA patient referrals and nodule management of stage IV lung cancer patients was conducted in seven Danish lung cancer investigation centers, covering four of the five Danish health regions. CT scans were performed up to 2 years before the patients' diagnosis from 2019 to 2021. Results: CT usage has increased steadily in Denmark over the past decade, with a simultaneous increase in the proportion of early-stage lung cancers, particularly stage IA. However, one Danish health region, Region Zealand, exhibited lower rates of early-stage lung cancer and overall survival despite a CT usage roughly similar to that of the other health regions. The audit did not find significant differences in pulmonary nodule management or a higher number of missed nodules by radiologists in this region compared to others. Conclusion: This study suggests that a high CT scan volume alone is not sufficient for the early detection of lung cancer. Factors beyond hospital management practices, such as patient-related delays in socioeconomically disadvantaged areas, may contribute to regional differences in survival rates. This has implications for future strategies for reducing these differences.

Increased use of computed tomography in Denmark: stage shift toward early stage lung cancer through incidental findings.

BACKGROUND: Computed tomography (CT) examinations are increasingly used worldwide and incidental findings are growing likewise. Lung cancer stage at diagnosis is pivotal to survival. The earliest stage of lung cancer, stage IA is in most cases asymptomatic. Potentially, increased use of clinical CTs could induce a stage shift toward earlier lung cancer diagnosis. MATERIALS AND METHODS: Data on the number of CT thorax in Denmark and the stage distribution of Danish lung cancer patients 2013-2020 were acquired from, respectively, the Danish Health Data Authority and the Danish Lung Cancer Registry. Clinical auditing of stage IA lung cancer patients was performed in the period 2019-2021 in a Danish region to assess the reasons for referral. Auditing of stage IV lung cancer patients was done to see whether a CT thorax was performed in a two-year period before diagnosis. RESULTS: All regions showed an increase in CTs per 1000 inhabitants. However, the number of CTs performed in 2013 differed by more than 50% among regions, and the increase per year also differed, from an increase of 1.9 to 3.4 more examinations per year. A significant correlation between CTs and fraction of stage IA lung cancers was seen in four out of the five regions. The audit of stage IA lung cancer cases revealed that 86.8% were incidental findings. Audit of stage IV lung cancer found that 4.3% had a nodule/infiltrate on a previous CT within a 2-year period prior to the diagnosis of lung cancer that was the probable origin of stage IV lung cancer. CONCLUSION: The study found that the vast majority of early-stage lung cancers were incidental findings. It highlights that follow-up algorithms of incidental findings should be used in accordance with guidelines and it should be unequivocally how the CT follow-up of pulmonary infiltrates is managed.

Augmented reality glasses as a new tele-rehabilitation tool for home use: patients' perception and expectations.

MATERIALS AND METHODS: A qualitative approach was employed to track perspectives from a range of patients with chronic lung and/or heart diseases. COPD, IPF and MI outpatients from Denmark and Finland were invited to participate. Data were collected through focus group and semi-structured in-depth interviews. Qualitative analysis was performed using standard thematic analytical approaches. A topic guide was used to explore experiences and perceptions of the ARG telerehabilitation device among participants. RESULTS: Thirteen patients (4 MI, 2 IPF and 7 COPD), 3 women and 10 men aged 56 to 75 years (mean age 63.3 years) were allocated into one focus group (9 patients) and 4 interviews (4 patients). Twelve patients reported the added value of ARG and suggested constructive changes such as the adjustable screen/brightness, robust head fixation for exercise performance, easy to navigate interface and supported feedback based on exercise performance. CONCLUSION: Patients with chronic heart or lung diseases described the added value in an ARG telerehabilitation programme. Improvements for a future version of the ARG were suggested.IMPLICATIONS FOR REHABILITATIONPatients with chronic pulmonary and heart diseases have difficulties to change behaviour to a more active and healthy lifestyle, offers from the health sector to participate in rehabilitation programmes at the hospital are feasible and improves quality of life and exercise capacity. Not all the patients are capable of participating in such rehabilitation programmes due to frailty and long distance to the hospital. Telerehabilitation seems to be a potential treatment to cope with the needs expressed above.Patient involvement in the development of a telerehabilitation solution to empower chronic pulmonary and heart patients to train, ensures a positive contribution to the design of the expected augmented reality software and hardware envisioned solution for telerehabilitation.The development of a user-centered telerehabilitation platform responding to the preferences of patients with chronic disease will remove barriers that limit use and compliance and improve empowerment in future research projects.

Persistent cough - A rare presentation of hepatocellular carcinoma.

Coughing is a very common condition, accounting for frequent visits in general practice. In this case report, we found the cause of persisting cough to be hepatocellular carcinoma, located in close proximity to the diaphragm. After the tumor had been treated with chemoembolization the coughing disappeared. After the common causes for persistent cough has been ruled out, the clinician could consider other, rarer, conditions as the cause of the coughing, including affection of the diaphragm.

Screening tools for evaluation of depression in Chronic Obstructive Pulmonary Disease (COPD). A systematic review.

Background: Anxiety and depression are common comorbid disorders in patients with chronic obstructive pulmonary disease (COPD), though estimates of their prevalence vary considerably. Depressive symptoms/depression are important comorbidities in COPD and an increasing interest is shown to these disorders. Depression may lead to reduced quality of life and increased morbidity and mortality. These statements underline the importance of implementing the use of screening instruments for depressive symptoms in a clinical setting. This systematic review evaluates four commonly used screening tools for depression in COPD. Furthermore we assess the prevalence of depression in COPD in the evaluated studies. Design: A literature search identified studies dealing with screening for depression in patients with COPD. We focused on the instruments: Beck Depression Inventory, Geriatric depression scale, Centre for Epidemiological Studies scale on Depression and Hospital and Anxiety Depression Scale. Results: Overall prevalence of depression was 30%. Demographic variations and severity of COPD influenced prevalence. The inter-prevalence of the four screening tools was consistent. We found a low variation between studies using the same tool. Few studies used control groups or compared the screening tool to a psychiatrist evaluation. Conclusions: This article calls for further investigation of the association between COPD and depressive symptoms. The subject is highly relevant for everyday life of patients with COPD and attention needs to be drawn to this issue in both an out- and in-patients.

Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group.

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF.

A review of wave mechanics in the pulmonary artery with an emphasis on wave intensity analysis.

Mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) remain the most common haemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, PVR only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness, and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension, and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery.

Method for a homogeneous distribution of pollens in an environmental exposure chamber.

BACKGROUND: A variety of different environmental exposure chambers (EECs) have been used to evaluate treatments for allergic rhinitis. OBJECTIVE: To describe and test a system for a homogenous distribution of grass pollen, Phleum Pratense, in an EEC to be used for controlled pollen exposure studies in allergic participants. METHODS: A chamber made of stainless steel with completely rounded corners, seating four individuals at a time, was used. Room pressure, temperature, humidity and the air change rate were kept constant throughout the study period. A rotating pipette dispensed a uniform supply of pollen into a turntable's v-shaped grooves. A stainless steel capillary tube sucked the pollens into a venturi throat at which time the pollens were mixed with a high-pressure airstream of compressed high-efficiency particulate arrestance filtered air and then transported to a spreading plate inside the EEC. To achieve uniform concentrations in the EEC, the turntable's rotating speed was continuously adjusted using information from video-coupled feedback and feed forward mechanisms. Pollen levels were detected using standard volumetric air samplers and laser particle counters. The target pollen exposure level was 1000 pollens/m(3) . Twenty-one participants were exposed to pollens in the EEC twice for 210 min. Participants evaluated their symptoms every 30 min using a total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching and sneezing. RESULTS: Across fifteen study days, the average pollen level was 982 pollens/m(3) (SD, 102 pollens/m(3) ). On average, participants experienced a 10% difference in overall pollen levels between their two visits to the EEC. The mean TNSSs rose throughout the exposure period, with a low at baseline of 0.43 (SD, 0.68) to a high of 4.71 (SD, 2.43) just before exiting the EEC. CONCLUSION AND CLINICAL RELEVANCE: This EEC provides a reproducible, precise and homogenous distribution of pollens making it suitable for single-centre allergy clinical trials.

First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus fumigatus isolates from azole-naive patients in Denmark despite negative findings in the environment.

Azole-resistant Aspergillus fumigatus harboring the TR34/L98H or TR46/Y121F/T289A alterations is increasingly found in Europe and Asia. Here, we present the first clinical cases of TR46/Y121/T289A and three cases of TR34/L98H outside the cystic fibrosis (CF) population in Denmark and the results of environmental surveys. Four patients (2012 to 2014) with 11 A. fumigatus and 4 Rhizomucor pusillus isolates and 239 soil samples (spring 2010 and autumn 2013, respectively) with a total of 113 A. fumigatus isolates were examined. Aspergillus isolates were screened for azole resistance using azole-containing agar. Confirmatory susceptibility testing was done using the EUCAST microbroth dilution EDEF 9.1 reference method. For relevant A. fumigatus isolates, CYP51A sequencing and microsatellite genotyping were performed. Three patients harbored TR34/L98H isolates. Two were azole naive at the time of acquisition and two were coinfected with wild-type A. fumigatus or R. pusillus isolates, complicating and delaying diagnosis. The TR46/Y121F/T289A strain was isolated in 2014 from a lung transplant patient. Genotyping indicated that susceptible and resistant Aspergillus isolates were unrelated and that no transmission between patients occurred. Azole resistance was not detected in any of the 113 soil isolates. TR34/L98H and TR46/Y121F/T289A alterations appear to be emerging in the clinical setting in Denmark and now involve azole-naive patients. Two recent soil-sampling surveys in Denmark were unable to indicate any increased prevalence of azole-resistant A. fumigatus in the environment. These findings further support the demand for real-time susceptibility testing of all clinically relevant isolates and for studies investigating the seasonal variation and ecological niches for azole-resistant environmental A. fumigatus.

Pulmonary apelin levels and effects in rats with hypoxic pulmonary hypertension.

BACKGROUND: The peptide apelin is localised in the vascular endothelium and highly expressed in pulmonary tissue. The aim of this study was to investigate whether apelin could be a potential lung-derived plasma marker for pulmonary hypertension, and study the effect of apelin in pulmonary arteries. METHODS: Apelin protein levels were measured in the lung, right ventricle, and plasma from normoxic and chronic hypoxic rats with pulmonary hypertension. Isolated intrapulmonary arteries were mounted in microvascular myographs and the effect of apelin investigated. Finally, the distribution of apelin receptors in pulmonary tissue was visualised by immunohistochemistry. RESULTS: Total pulmonary apelin content was not changed by hypoxia. Right ventricular apelin concentrations and content were lower than in the lung, but increased substantially in hypoxia in correlation with right ventricular pressure. Plasma apelin did not reflect pulmonary or right ventricular apelin levels. In pulmonary arteries from normoxic rats, apelin inhibited vasoconstriction to endothelin-1 and angiotensin-II. However, in arteries from hypoxic rats, apelin failed to inhibit contraction to angiotensin-II and endothelin-1. No difference in immunoreaction for apelin receptors was found in lung sections and arteries from normoxic versus chronic hypoxic rats. CONCLUSIONS: Apelin changes in the right ventricle seem more specific for pulmonary hypertension than do changes in pulmonary tissue, which does not speak in favour of apelin as a lung-derived marker for this disease. During normoxic conditions, apelin has a modulating effect on vasoconstriction which is lost in chronic hypoxia. This may reflect alterations in the signal transduction downstream of the apelin receptor.

Flextube reflectometry for level diagnosis in patients with obstructive sleep apnoea and snoring.

The aim of this study was to use sound reflections in a flexible tube (flextube reflectometry) for identifying the predominant obstructive level of the upper airway in a series of patients referred to a sleep clinic. We also wished to study the relationship between the number of flextube narrowings per hour recording and the RDI (respiratory disturbance index = apnoeas and hypopneas per hour recording) by ResMed AutoSet (AS), which is a device based on nasal pressure variations. We performed sleep studies on 54 patients referred for snoring or OSA; 1) at home with AS; 2) in hospital using flextube reflectometry and AS simultaneously. The predominant obstructive level of the upper airway was retropalatal in 15 of the patients and retrolingual in 25 of the patients determined by flextube reflectometry. In 14 there was no predominant level of narrowing. We found a statistically significant correlation between the number of flextube narrowings per hour recording and the RDIs by the AS (Spearman's correlation coefficient r = 0.62, p < 0.001, n = 54). Flextube reflectometry may provide useful information regarding the level of obstructive predominance during obstructive events. The method also determines the frequency of respiratory disturbances and records snoring sound.

Flextube reflectometry and pressure-recordings for level diagnosis in obstructive sleep apnoea.

The objective of this study was to compare sound reflections in a flexible tube (flextube reflectometry) with pressure-catheter recordings (ApneaGraph) for identifying the predominant obstructive level of the upper airway during sleep. Seventeen males with suspected obstructive sleep apnoea syndrome (OSAS) were included in the study. The mean (standard deviation = SD) number of flextube narrowings per hour recording was 50.2 (20.4) and the mean (SD) RDI (respiratory disturbance index = apnoeas and hypopnoeas per hour recording) determined by the ApneaGraph was 45.7 (20.2). The mean difference (SD) between the number of flextube narrowings per hour recording and the RDIs determined by the ApneaGraph was not statistically significantly different from 0. There was no statistically significant correlation between the percentage of retropalatal narrowing of the total narrowing (retropalatal and retrolingual narrowing) measured by flextube reflectometry and the percentage of retropalatal ("upper") obstructive apnoeas and hypopnoeas of the total number ("upper", "intermediate" and "lower") measured by ApneaGraph (Spearman's correlation coefficient r = 0.24, p = 0.36, N = 17). In conclusion diverging results were found in flextube reflectometry studies and pressure-recordings performed on different nights regarding the level distribution of obstructions during sleep. Possible explanations of this discrepancy are discussed.

The occurrence of sinusitis in HIV-infected patients with fever.

Sinusitis is commonly occurring in patients infected with Human Immunodeficiency Virus I (HIV), but the occurrence and etiology have not been established. The purpose of this study was prospectively to determine the occurrence, site and type of paranasal sinus abnormalities seen on MRI in HIV-infected patients with fever, to relate the abnormalities to clinical and immunological parameters, and to determine the microbiological agents found in the sinus aspirates. MRI was performed in 54 HIV-infected patients with 70 evaluable episodes of fever. Patients receiving antibiotics were excluded. Bactrim was permitted, when given as prophylaxis of Pneumocystis carinii pneumonia. If abnormalities were found on MRI, sinus aspiration was performed and the aspirate investigated. MRI abnormalities were found in 54.3% of the patients with a significantly higher occurrence of pathological changes in AIDS patients compared with HIV-infected without AIDS. In approximately 2/3 of the aspirates a probable, etiologic agent was found. However, 1/3 of these agents were atypical such as cytomegalovirus and mycobacteriae; in one patient Non-Hodgkin's lymphoma was found. The high occurrence of sinusitis in HIV-infected patients and the atypical findings in the sinus aspirates stress the importance of searching for sinusitis and the etiology to ensure the correct treatment.

Flextube reflectometry for localization of upper airway narrowing--a preliminary study in models and awake subjects.

The aim of this study was to examine an acoustic reflection method using a flexible tube for identifying the obstructive site of the upper airway in snorers and patients with obstructive sleep apnoea (OSA). As a preliminary study it was performed n models and subjects in the awake state. Flextube narrowing was produced in a model of the nose and pharynx and three blinded observers assessed the obstructive level. The correlation between pharyngeal narrowing assessed by endoscopy and by acoustic measurement during Müller manoeuvres was also examined in 10 OSA patients and 11 healthy non-snoring, adults. Three blinded observers dentified the level of 176 of 180 random cases of flextube narrowing in a polycarbonate model correctly The level of narrowing was always correctly evaluated within 1.9 mm. Pharyngeal area decrease was measured by the flextube method during the Müller manoeuvre but it was not closely related to the findings by endoscopy. In conclusion the flextube reflectometry method was able to demonstrate narrowng in a model of the nose and pharynx in a precise way. Narrowing was also observed during Müller manoeuvres. Flextube reflectometry may be a promising method to detect upper airway narrowing but further evaluation during sleep is required.

Flextube reflectometry for determination of sites of upper airway narrowing in sleeping obstructive sleep apnoea patients.

The aim of this study was to examine a new technique based on sound reflections in a flexible tube for identifying obstructive sites of the upper airway during sleep. There was no significant difference between two nights in seven obstructive sleep apnoea (OSA) patients regarding the level distribution of pharyngeal narrowings, when the pharynx was divided into two segments (retropalatal and retrolingual). We also compared the level distribution determined by magnetic resonance imaging (MRI) with the level distribution found by flextube reflectometry in seven OSA patients. There was no significant difference between flextube and MRI level distributions during obstructive events, but due to few subjects the power of the test was limited. We found a statistically significant correlation between the number of flextube narrowings per hour of sleep and the number of obstructive apnoeas and hypopnoeas per hour of sleep determined by polysomnography (PSG) in 21 subjects (Spearman's correlation coefficient r = 0.79, P < 0.001). In conclusion, the flextube reflectometry system seems to be useful for level diagnosis in OSA before and after treatment.

Acoustic rhinometry: validation by three-dimensionally reconstructed computer tomographic scans.

The aim of the present study was a validation of acoustic rhinometry (AR) by computed tomography (CT). Six healthy subjects were examined by CT and AR. The CT data were processed in a computer program (AutoCAD), and a virtual three-dimensional model of each nasal cavity was constructed. This model permitted an individual prediction of the center line of the sound wave propagation through the air volume of the nasal cavity with the cross-sectional areas oriented perpendicularly to this line. The area-distance curves derived from AR and CT were compared. Linear regression analysis revealed a reasonable agreement of AR and CT in the anterior nose below a mean of 6 cm distance from the nostrils [r = 0.839, P < 0.01, m = 1.123, b = -0.113 (AR = m x CT + b)]. The measuring accuracy using CT as gold standard revealed a mean error at the nasal valve of <0.01 cm(2) (4.52%) and at the nasal isthmus of 0.02 cm(2) (1. 87%). Beyond 6 cm, the correlation decreased (r = 0.419), and overestimation of the true area occurred (>100%). In conclusion, the measurements were reasonably accurate for diagnostic use up to the turbinate head region. Certain factors induce an overestimation of the true areas beyond this region. However, these factors are constant and reproducible in a single subject, and intraindividual comparative measurements are possible beyond the turbinate head region.

Acoustic rhinometry: recommendations for technical specifications and standard operating procedures.

This document is the result of the work and discussion of the Standardization Committee on Acoustic Rhinometry and presents guidelines for quality control and optimal application of acoustic rhinometry at its present stage. It is suggested that: 1. A well-defined standard nose is used for testing and optimising the equipment (data for a standard nose is given in the paper). 2. Procedures for evaluation of accuracy and repeatability of the measurements in the standard nose are presented, and error limits are defined for the area-distance curve as a whole, for the minimum cross-sectional area and for the volume from 0-5 cm into the nose. 3. Publication of results should include the volume 0-5 cm into the nose (volume from 2-5 cm for mucosal changes) the minimum cross-sectional area or preferably the two first minima and the distances to those areas. 4. The operator should be trained, follow a standard operating procedure and the environmental conditions (temperature and noise) be controlled. 5. Attention should be given to the nosepiece and the coupling between the equipment and the nose to obtain correct position, and sufficient seal without disturbing the anatomy. 6. The manufacturer should give information about the performance of the equipment, calibration procedures and maintenance, hygiene, environmental and safety standards.