Advances in Respiratory Medicine

Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training (n = 115,145) and validation datasets (n = 13,017). The remaining cohort with missing values (n = 394,779) was then combined with the primary lung tumour datasets (n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78–0.79) and 0.78 (95%CI = 0.77–0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757–0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning. Full article

Tuberculosis (TB) affects a third of the global population, and a large population of infected individuals still remain undiagnosed—making the visible burden only the tip of the iceberg. The detection of tuberculosis in close-proximity patients is one of the key priorities for attaining the Sustainable Development Goals (SDG) of TB elimination by 2030. With the current battery of screening tests failing to cover this need, the authors of this paper examined a simple and inexpensive point-of-care breath analyzer (TSI-3000(I)), which is based on detecting the volatile organic compounds that are emitted from infected cells and released in exhaled breath as a screening tool for the detection of TB. A single-center pilot study for assessing the diagnostic accuracy of the point-of-care Tuberculosis Breath Analyzer was conducted, and it was compared against the WHO-recommended TrueNat assay, which is a rapid molecular test and was also treated as the reference standard in this study. Of the 334 enrolled participants with TB signs/symptoms, 42.51% were TrueNat positive for Mycobacterium tuberculosis. The sensitivity of the Tuberculosis Breath Analyzer was found to be 95.7%, with a specificity of 91.3% and a ROC area of 0.935. The test kit showed considerable/significant high sensitivity and specificity as reliability indicators. The performance of the Tuberculosis Breath Analyzer tested was found to be comparable in efficiency to that of the TrueNat assay. A large cohort-based multicentric study is feasibly required to further validate and extrapolate the results of the pilot study. Full article

Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting β2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile. Full article

The aim of this publication is to analyze the topic of high-frequency jet ventilation (HFJV), namely catheter HFJV (C-HFJV), from a mathematical–physical as well as a clinical point of view. There are known issues with applying anesthesia and artificial lung ventilation (ALV) during surgical procedures in the upper airways, e.g., during bronchoscopy or tracheostomy. The principles, advantages, and disadvantages of HFJV are discussed in context with basic physical principles to clarify the proper use of this method. The basic technical principles of catheter construction, as well as its functional properties from a biophysical point of view, are introduced. Also, the placement of the catheter in the airways, the set-up of the HFJV ventilator, and the indications as well as the risks and contraindications of the use of C-HFJV are analyzed. This leads to the explanation of potentially optimal techniques for C-HFJV applications. In this article, we present the positive effects of C-HFJV even with complications such as bacterial or viral pneumonia, including COVID-19. In conclusion, we offer recommendations for clinical practice obtained from a literature review and from our rich clinical experience. Full article

Background: In 2018, GOLD addressed the issues of genotypes associated with risk factors for COPD. The genome-wide association study (GWAS) demonstrated an association between COPD and several genetic variants of single nucleotide polymorphisms (SNPs) of the FAM13A gene with the risk of COPD. Objective: To study the single nucleotide polymorphisms rs2869967 and rs17014601 of the FAM13A gene in chronic obstructive pulmonary disease. Subjects and research methods: 80 subjects diagnosed with COPD and 80 subjects determined not to have COPD according to GOLD 2020 criteria; the subjects were clinically examined, interviewed, and identified as possessing single nucleotide polymorphisms using the sanger sequencing method on whole blood samples. Results: The male/female ratio of the patient group and the control group was 79/1 and 39/1, respectively. The percentages of C and T alleles of rs2869967 in COPD patients were 50.6% and 49.4%, respectively. The percentages of C and T alleles of rs17014601 in COPD patients were 31.9% and 68.1%, respectively. At rs17014601, the ratio values of alleles T and C in the disease group and the control group were markedly different, making them statistically reliable (p = 0.031). The rate of CT genotype in the group of patients was considerably higher than that of the control group. The TT homozygous genotype had a lower risk of COPD compared with the other genotypes in the dominant model (ORTT/(CC + CT) = 0.441; CI95% = 0.233–0.833); this difference was statistically significant (p = 0.012). Conclusions: With rs17014601, it is characteristic that the frequency of the T allele appears more than the C allele, and the CT heterozygous phenotype accounts for the highest proportion in rs17014601 and rs2869967 recorded in COPD patients. There is an association between the genetic variant of the SNP FAM13A-rs17014601 and the risk of COPD. Full article

Background: Medication adherence in asthmatic patients enhances the effectiveness of treatments, but some studies in low and middle-income countries still show some limitations. Our study aimed to determine if pharmacist-led interventions could increase medication adherence, improve treatment effectiveness, and relieve symptom severity in outpatients with asthma. Methods: We conducted a randomized, controlled trial on 247 asthmatic outpatients (aged ≥ 16) with a 1:1 ratio randomization at the hospitalization time and repeated after 1-month discharge. The primary outcome was to detect the difference in medication adherence between groups. Adherence was assessed by the general medication adherence scale (GMAS). Data collected by questionnaire was coded and entered into SPSS_20 for statistical analysis; Results: 247 patients (123 intervention, 124 control) were enrolled (61.1% male). After intervention, the adherence rate was higher among the intervention group than the control group (94.3% vs. 82.8%, p = 0.001). Patient behavior and knowledge were enhanced in the intervention group (p < 0.05). Asthma symptoms were relieved in the intervention group (p = 0.014). Pharmacist-led interventions on adherence rate were higher with OR: 3.550, 95% CI: 1.378–9.143, p = 0.009. Conclusions: pharmaceutical intervention could improve medication adherence, treatment efficacy, and the outcome should not be taken for granted; further research should be carried out in this regard. Full article

Background: Exercise-induced bronchoconstriction (EIB) is a common problem in elite athletes. Classical pathways in the development of EIB include the osmotic and thermal theory as well as the presence of epithelial injury in the airway, with local water loss being the main trigger of EIB. This study aimed to investigate the effects of systemic hydration on pulmonary function and to establish whether it can reverse dehydration-induced alterations in pulmonary function. Materials and Methods: This follow-up study was performed among professional cyclists, without a history of asthma and/or atopy. Anthropometric characteristics were recorded for all participants, and the training age was determined. In addition, pulmonary function tests and specific markers such as fractional exhaled nitric oxide (FeNO) and immunoglobulin E (IgE) were measured. All the athletes underwent body composition analysis and cardiopulmonary exercise testing (CPET). After CPET, spirometry was followed at the 3rd, 5th, 10th, 15th, and 30th min. This study was divided into two phases: before and after hydration. Cyclists, who experienced a decrease in Forced Expiratory Volume in one second (FEV₁) ≥ 10% and/or Maximal Mild-Expiratory Flow Rate (MEF_25–75) ≥ 20% after CPET in relation to the results of the spirometry before CPET, repeated the test in 15-20 days, following instructions for hydration. Results: One hundred male cyclists (n = 100) participated in Phase A. After exercise, there was a decrease in all spirometric parameters (p < 0.001). In Phase B, after hydration, in all comparisons, the changes in spirometric values were significantly lower than those in Phase A (p < 0.001). Conclusions: The findings of this study suggest that professional cyclists have non-beneficial effects on respiratory function. Additionally, we found that systemic hydration has a positive effect on spirometry in cyclists. Of particular interest are small airways, which appear to be affected independently or in combination with the decrease in FEV₁. Our data suggest that pulmonary function improves systemic after hydration. Full article

A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased incidence of drug-resistant pathogens (DRP) in patients from a community with pneumonia, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Research has been published attempting to identify DRP in CAP through the implementation of probabilistic approaches in clinical practice. However, recent epidemiological data showed that the incidence of DRP in CAP varies significantly according to local ecology, healthcare systems and countries where the studies were performed. Several studies also questioned whether broad-spectrum antibiotic coverage might improve outcomes in CAP, as it is widely documented that broad-spectrum antibiotics overuse is associated with increased costs, length of hospital stay, drug adverse events and resistance. The aim of this review is to analyze the different approaches used to identify DRP in CAP patients as well as the outcomes and adverse events in patients undergoing broad-spectrum antibiotics. Full article

Lung ultrasound has become a part of the daily examination of physicians working in intensive, sub-intensive, and general medical wards. The easy access to hand-held ultrasound machines in wards where they were not available in the past facilitated the widespread use of ultrasound, both for clinical examination and as a guide to procedures; among point-of-care ultrasound techniques, the lung ultrasound saw the greatest spread in the last decade. The COVID-19 pandemic has given a boost to the use of ultrasound since it allows to obtain a wide range of clinical information with a bedside, not harmful, repeatable examination that is reliable. This led to the remarkable growth of publications on lung ultrasounds. The first part of this narrative review aims to discuss basic aspects of lung ultrasounds, from the machine setting, probe choice, and standard examination to signs and semiotics for qualitative and quantitative lung ultrasound interpretation. The second part focuses on how to use lung ultrasound to answer specific clinical questions in critical care units and in emergency departments. Full article

Invasive pulmonary aspergillosis (IPA) presents a known risk to critically ill patients with SARS-CoV-2; quantifying the global burden of IPA in SARS-CoV-2 is extremely challenging. The true incidence of COVID-19-associated pulmonary aspergillosis (CAPA) and the impact on mortality is difficult to define because of indiscriminate clinical signs, low culture sensitivity and specificity and variability in clinical practice between centers. While positive cultures of upper airway samples are considered indicative for the diagnosis of probable CAPA, conventional microscopic examination and qualitative culture of respiratory tract samples have quite low sensitivity and specificity. Thus, the diagnosis should be confirmed with serum and BAL GM test or positive BAL culture to mitigate the risk of overdiagnosis and over-treatment. Bronchoscopy has a limited role in these patients and should only be considered when diagnosis confirmation would significantly change clinical management. Varying diagnostic performance, availability, and time-to-results turnaround time are important limitations of currently approved biomarkers and molecular assays for the diagnosis of IA. The use of CT scans for diagnostic purposes is controversial due to practical concerns and the complex character of lesions presented in SARS-CoV-2 patients. The key objective of management is to improve survival by avoiding misdiagnosis and by initiating early, targeted antifungal treatment. The main factors that should be considered upon selection of treatment options include the severity of the infection, concomitant renal or hepatic injury, possible drug interactions, requirement for therapeutic drug monitoring, and cost of therapy. The optimal duration of antifungal therapy for CAPA is still under debate. Full article

Pulmonary embolismis an acute disease with chronic complications and, although it is not considered a chronic disease, it requires close follow-up. The scope of the present literature review is to decode the existing data concerning quality of life and the mental health impact of PE during the acute and long-term phases of the disease. The majority of studies reported impaired quality of life in patients with PE when compared to population norms, both in the acute phase and >3 months after PE. Quality of life improves over time, irrespectively of the measurement used. Fear of recurrences, elderly, stroke, obesity, cancer and cardiovascular comorbidities are independently associated with worse QoL at follow-up. Although disease specific instruments exist (e.g., the Pulmonary Embolism Quality of Life questionnaire), further research is required in order to develop questionnaires that may fulfil international guideline requirements. The fear of recurrences and the development of chronic symptoms, such as dyspnea or functional limitations, may further impair the mental health burden of PE patients. Mental health may be implicated by post-traumatic stress disorder, anxiety and depressive symptoms present following the acute event. Anxiety may persist for 2 years following diagnosis and may be exaggerated by persistent dyspnea and functional limitations. Younger patients are at higher risk of anxiety and trauma symptoms while elderly patients and patients with previous cardiopulmonary disease, cancer, obesity or persistent symptoms exhibit more frequently impaired QoL. The optimal strategy for the assessment of mental health in this patient pool is not well defined in the literature. Despite mental burden being common following a PE event, current guidelines have not incorporated the assessment or management of mental health issues. Further studies are warranted to longitudinally assess the psychological burden and elucidate the optimal follow-up approach. Full article

Introduction: Idiopathic multicentric Castleman disease (MCD) has been reported to form lung cysts at a relatively high rate. However, the radiological and pathological features of cystic formation in MCD are unclear. Methods: To clarify these questions, we retrospectively investigated the radiological and pathological findings of cysts in MCD patients. Eight consecutive patients who underwent surgical lung biopsies in our center from 2000 to 2019 were included. Results: The median age was 44.5 years, with three males and five females. On the initial computed tomography, cyst formation was found in seven patients (87.5%). All of the cysts were multiple, round, and thin walled, accompanying ground-glass attenuation (GGA) around cysts. In six patients (75%), cysts increased during their clinical courses, and the new cysts had emerged from GGA, although GGA was improved by treatment. In all four cases, whose pulmonary cysts could be pathologically evaluated, a marked plasma cell infiltration around the cyst wall, and loss of elastic fibers of the alveolar wall were observed. Conclusions: Pulmonary cysts emerged in the area of GGA pathologically consistent with plasma cell infiltration. Cysts in MCD may be formed by the loss of elastic fibers due to marked plasma cell infiltration and may be considered irreversible changes. Full article

Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions. Full article

In recent years, the pathogenic role and antibiotic resistance of methicillin-resistant Staphylococcus aureus (MRSA) strains causing severe community-acquired pneumonia (CAP) have received increasing attention in clinical practice. The aim of this study was to determine the rate of isolates of MRSA strains causing severe CAP in children and to assess their level of antibiotic resistance. The study design was cross-sectional. Children with severe CAP were sampled by nasopharyngeal aspiration for the culture, isolation, and identification of MRSA. Antimicrobial susceptibility testing was performed using the gradient diffusion method to determine the minimum inhibitory concentration (MIC) of antibiotics. Results: MRSA was identified as the second leading cause of severe CAP in Vietnamese children. The rate of isolates of S. aureus was 41/239 (17.5%), of which most were MRSA, at 32/41 (78.0%). MRSA strains were completely non-susceptible to penicillin (100%), more resistant to clindamycin and erythromycin, less sensitive to ciprofloxacin and levofloxacin, and fully susceptible to vancomycin and linezolid, with a 32-fold decreased MIC₉₀ for vancomycin (0.5 mg/L) and a 2-fold decreased MIC₉₀ for linezolid (4 mg/L). Therefore, vancomycin and linezolid may be appropriate options for severe CAP identified by MRSA. Full article

Patients with COPD (chronic obstructive pulmonary disease) are at a higher risk of comorbid conditions such as anxiety and/or depression, which in turn increase their symptom burden and rehospitalizations compared to the general population. It is important to investigate the pathophysiology and clinical implications of mental health on patients with COPD. This review article finds that COPD patients with anxiety and/or depression have a higher rehospitalization incidence. It reviews the current screening and diagnosis methods available. There are pharmacological and non-pharmacologic interventions available for treatment of COPD patients with depression based on severity. COPD patients with mild depression benefit from pulmonary rehabilitation and cognitive behavioral therapy, whereas patients with severe or persistent depression can be treated with pharmacologic interventions. Full article

Heart failure (HF) is a multidisciplinary disease affecting almost 1–2% of the adult population worldwide. Symptoms most frequently reported by patients suffering from HF include dyspnoea, cough or exercise intolerance, which is equally often observed in many pulmonary diseases. The spectrum of lung changes related to HF is wide. The knowledge of different types of these abnormalities is essential to distinguish patients with HF from patients with lung diseases or both disorders and thus avoid unnecessary diagnostics or therapies. In this review, we aimed to summarise recent research concerning the spectrum of lung abnormalities related to HF in three frequently used lung imaging techniques: chest X-ray (CXR), lung ultrasound (LUS) and chest computed tomography (CT). We discussed the most prevalent abnormalities in the above-mentioned investigations in the context of consecutive pathophysiological stages identified in HF: (i) redistribution, (ii) interstitial oedema, and (iii) alveolar oedema. Finally, we compared the utility of these imaging tools in the clinical setting. In conclusion, we consider LUS the most useful and promising imaging technique due to its high sensitivity, repeatability and accessibility. However, the value of CXR and chest CT is their potential for establishing a differential diagnosis. Full article

End-stage kidney disease (ESKD) exposes patients to progressive physical deconditioning involving the respiratory muscles. The aim of this pilot randomized controlled trial was to determine the feasibility and effectiveness of low-intensity respiratory muscle training (RMT) learned at the hospital and performed at home. A group of ESKD patients (n = 22) were randomized into RMT or usual care (control group, CON) in a 1:1 ratio. The respiratory training was performed at home with an inspiratory–expiratory system for a total of 5 min of breathing exercises in a precise rhythm (8 breaths per minute) interspersed with 1 min of rest, two times per day on nondialysis days for a total of 4 weeks, with the air resistance progressively increasing. Outcome measures were carried out every 4 weeks for 3 consecutive months, with the training executed from the 5th to the 8th week. Primary outcomes were maximal inspiratory and expiratory pressure (MIP, MEP), while secondary outcomes were lung capacity (FEV1, FVC, MVV). Nineteen patients without baseline between-group differences completed the trial (T: n = 10; Age: 63 ± 10; Males: n = 12). Both MIP and MEP significantly improved at the end of training in the T group only, with a significant difference of MEP of 23 cmH₂O in favor of the RMT group (p = 0.008). No significant variations were obtained for FVC, FEV1 or MVV in either group, but there was a greater decreasing trend over time for the CON group, particularly for FVC (t = −2.00; p = 0.046). Low-fatiguing home-based RMT, with a simple device involving both inspiratory and expiratory muscles, may significantly increase respiratory muscle strength. Full article

Background: Patients with respiratory disorders often have additional diseases and are usually treated with more than one medication to manage their respiratory conditions as well as additional comorbidities. Thus, they are frequently exposed to polypharmacy (≥5 drugs), which raises the risk for drug–drug interactions (DDIs) and adverse drug reactions (ADRs). In this work, we present the results regarding the prevalence of DDIs in hospitalized patients with respiratory disorders in Greece. Methods: A 6-month descriptive single-center retrospective observational study enrolled 102 patients with acute or chronic respiratory disorders. Clinical characteristics and medication regimens were recorded upon admission, hospitalization, and discharge. The prevalence of DDIs and their clinical significance was recorded and analyzed. Results: Unspecified acute lower respiratory tract infection (25%), exacerbations of chronic obstructive pulmonary disease (12%) and pneumonia (8%) were the most frequent reasons for admission. Cardiovascular disorders (46%), co-existing respiratory disorders (32%), and diabetes (25%) were the most prevalent comorbidities. Polypharmacy was noted in 61% of patients upon admission, 98% during hospitalization, and 63% upon discharge. Associated DDIs were estimated to be 55% upon admission, 96% throughout hospitalization, and 63% on discharge. Pharmacodynamic (PD) DDIs were the most prevalent cases (81%) and referred mostly to potential risk for QT-prolongation (31.4% of PD-DDIs) or modulation of coagulation process as expressed through the international normalized ratio (INR) (29.0% of DDIs). Pharmacokinetic (PK) DDIs (19% of DDIs) were due to inhibition of Cytochrome P450 mediated metabolism that could lead to elevated systemic drug concentrations. Clinically significant DDIs characterized as “serious-use alternative” related to 7% of cases while 59% of DDIs referred to combinations that could be characterized as “use with caution—monitor”. Clinically significant DDIs mostly referred to medication regimens upon admission and discharge and were associated with outpatient prescriptions. Conclusions: Hospitalized patients with respiratory disorders often experience multimorbidity and polypharmacy that raise the risk of DDIs. Clinicians should be conscious especially if any occurring arrhythmias, INR modulations, and prolonged or increased drug action is associated with DDIs. Full article

We aimed to evaluate asthmatic patients with fixed airways obstruction (FAO) and to verify the impact of follow-up in an asthma-dedicated outpatient clinic on symptoms control and spirometry compared to asthmatics without FAO. We enrolled 20 asthmatic FAO+ patients and 20 FAO− asthmatics at baseline (T0) and at a one-year follow-up visit (T1). FAO+ and FAO− groups were compared for anamnesis, FEV1, asthma control test (ACT) and their ΔT0–T1. FAO+ and FAO− groups did not differ for age, BMI, pack-years, allergy, T0 blood eosinophils, comorbidities or GINA therapy step at T0 and T1, whereas, in the FAO+ group, we found more patients with a delay >5 years between symptoms onset and correct asthma diagnosis (p < 0.05). ACT at T0 and ΔT0–T1, FEV1 at ΔT0–T1 and number of exacerbations at T0 and ΔT0–T1 did not differ between groups. Despite a widespread perception of FAO, per se, as a severity factor for asthma, we found similar severity profiles and amelioration after one year of treatment in the FAO+ and FAO− groups. The only factor linked to FAO development in our population was a delay in asthma diagnosis from respiratory symptoms onset, which may have led to airway remodeling. Physicians should characterize patients with FAO for avoiding misdiagnosis between asthma and other respiratory diseases and for establishing the appropriate therapy. Full article