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.

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.

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.

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.

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.

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.

Acoustic rhinometry: influence of paranasal sinuses.

The influence of the maxillary sinuses in acoustic rhinometry (AR) has not been evaluated, and this is the aim of the present study. We examined six subjects with AR and magnetic resonance imaging (MRI) after nasal decongestion to compare the area-distance relationships determined by the two methods. From the MRI data we obtained copies of the nasal cavities with and without maxillary sinuses, which were made in plastic by a stereolithographic method. AR curves from models without maxillary sinuses differed from AR curves with sinuses included but were in agreement with MRI curves without inclusion of sinuses. A similar difference in AR was seen in two subjects before and after the nasal cavities were flushed with saline to fill up the maxillary sinuses. The measured volume in the first 50 mm of the nasal cavity models was unaffected by the sinuses, but the volume in the first 70 mm corresponding to the length of the nasal cavity septum was increased slightly but significantly (from 10.8 to 11.3 cm3; P = 0.05). The presence of maxillary sinuses increased the volume of the epipharynx (70-100 mm from the nostril) from 12.2 to 21.3 cm3 (P < 0.01), and this increase was not due to the influence from the contralateral nasal cavity. We conclude that the maxillary sinuses may significantly contribute to the acoustically determined areas in the posterior part of the nasal cavity and the epipharynx, especially during decongestion, and may explain a part of the difference between area-distance curves obtained by AR and MRI, whereas contribution from the contralateral nasal cavity does not.

Nasal airway geometry: comparison between acoustic reflections and magnetic resonance scanning.

To evaluate the accuracy of the acoustic reflection (AR) technique for determination of nasal cavity cross-sectional areas, the area-distance function of both sides of the nose was determined in 10 subjects and compared with magnetic resonance imaging (MRI). Interindividual variation for the correlation between MRI and AR was seen, but in general the areas from 1 to 6 cm into the nasal cavity measured by AR were larger than areas measured by MRI, especially where the surface was most convoluted. The total volume for this region was 6.47 +/- 1.83 (SD) cm3 for AR and 5.65 +/- 1.34 cm3 for MRI. It was demonstrated that this could be due to errors in calculation of the areas on the basis of MRI and AR. In the posterior part of the nasal cavity and the epipharynx, there was a convincingly higher correlation between acoustic measurements and a scan perpendicular to the assumed geometrical axis of the epipharynx than between acoustic measurements and coronal scanning. This indicates that the sound axis roughly follows the geometrical axis. In a model of two tubes (nasal cavities) joined in a larger tube (the epipharynx), closure of the posterior part of the latter revealed that the contralateral nasal cavity is likely to cause overestimation of the posterior part of the epipharynx during AR compared with MRI.

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: evaluation of nasal cavity geometry by acoustic reflection.

To study the geometry of the nasal cavity we applied an acoustic method (J. Appl. Physiol. 43: 523-536, 1977) providing an estimate of cross-sectional area as a function of distance. Acoustic areas in a model constructed from a human nasal cast, in the nasal cavity of a cadaver and in 10 normal subjects and two patients with well-defined afflictions of the nasal cavity, were compared with similar areas obtained by computerized tomography (CT) scans, a specially developed water displacement method, and anterior rhinomanometry. We found a coefficient of variation of the areas of less than 2% by the acoustic method compared with 15% for the rhinomanometric measurements. Acoustic areas correlated highly to similar areas obtained by CT scanning (r = 0.94) and by water displacement (r = 0.96). In two patients the acoustic method accurately outlined, respectively, a tumor in the nose and a septum deviation. It is concluded that this method provides an accurate method for measuring the geometry of the nasal cavity. It is easy to perform and is potentially useful for investigation of physiological and pathological changes in the nose.

Acoustic reflections during rhinometry: spatial resolution and sound loss.

The accuracy of the acoustic reflections method for the evaluation of human nasal airway geometry is determined by the physical limitations of the technique and also by the in vivo deviations from the assumptions of the technique. The present study 1) examines the sound loss caused by nonrigidity of the nasal mucosa and viscous loss caused by complex geometry and its influence on the estimation of the acoustic area-distance function; 2) examines the optimal relation between sampling frequency and low-pass filtering, and 3) evaluates advantages of breathing He-O2 during the measurements on accuracy. Measurements made in eight plastic models, with cavities exactly identical to the "living" nasal cavities, revealed only minor effects of nonrigidity of the nasal mucosa. This was confirmed by an electrical analog model, based on laser vibrometry admittance measurements of the nasal mucosa, which indicated that the error in the acoustic measurements caused by wall motion is insignificant. The complex geometry of the nasal cavity per se (i.e., departure from circular) showed no significant effects on the measurements. Low-pass filtering of the signal is necessary to cut off cross modes arising in the nasal cavity. Computer simulations and measurements in models showed that the sampling frequency should be approximately four times the low-pass filtering frequency (i.e., twice the Nyquist frequency) to avoid influence on the result. No advantage was found for the the use of He-O2 vs. air in the nasal cavity.

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: evaluation of the nasal cavity with septal deviations, before and after septoplasty.

We introduce acoustic rhinometry as a new, objective method to assess the geometry of the nasal cavity. The cross-sectional area of the nasal cavity as a function of distance from the nostrils was obtained. A group of 21 patients with septal deformities was examined with acoustic rhinometry preoperatively and postoperatively. These values were compared with those of 21 normal control subjects. The minimal cross-sectional area (MCA) is located in the anterior part of the nose, and it shifts anteriorly under the effect of decongestion. The preoperative value of MCA is related to the location and severity of the anterior septal deformity. Postoperative smaller MCA found in the opposite side of that narrowed by a severe anterior septal deformity may be explained by the impact of septoplasty without reduction of a hypertrophic turbinate. A highly significant relation between MCA and the subjective feeling of nasal patency, before and after surgery, suggests that MCA is a valuable parameter to express nasal patency. Correction of posterior septal deformities is found to increase significantly the cross-sectional area posteriorly. The effect of decongestion in the postoperative values, however, suggests that the mucosa contributes even more to the cross-sectional area of the posterior part of the nose. Acoustic rhinometry seems very suitable for evaluation of the nasal cavity in cases where septoplasty and turbinoplasty is considered, as well as for the postoperative evaluation.