The Role of Lung Microbiome in Fibrotic Interstitial Lung Disease-A Systematic Review.

Interstitial Lung Disease (ILD) involves lung disorders marked by chronic inflammation and fibrosis. ILDs include pathologies like idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), hypersensitivity pneumonitis (HP) or sarcoidosis. Existing data covers pathogenesis, diagnosis (especially using high-resolution computed tomography), and treatments like antifibrotic agents. Despite progress, ILD diagnosis and management remains challenging with significant morbidity and mortality. Recent focus is on Progressive Fibrosing ILD (PF-ILD), characterized by worsening symptoms and fibrosis on HRCT. Prevalence is around 30%, excluding IPF, with a poor prognosis. Early diagnosis is crucial for optimizing outcomes in PF-ILD individuals. The lung microbiome comprises all the microorganisms that are in the respiratory tract. Relatively recent research try to evaluate its role in respiratory disease. Healthy lungs have a diverse microbial community. An imbalance in bacterial composition, changes in bacterial metabolic activities, or changes in bacterial distribution within the lung termed dysbiosis is linked to conditions like COPD, asthma and ILDs. We conducted a systematic review of three important scientific data base using a focused search strategy to see how the lung microbiome is involved in the progression of ILDs. Results showed that some differences in the composition and quality of the lung microbiome exist in ILDs that show progressive fibrosing phenotype. The results seem to suggest that the lung microbiota could be involved in ILD progression, but more studies showing its exact pathophysiological mechanisms are needed.

COVID-19 "Nightmare": Perceived Stress, Emotional Distress, and Burnout Syndrome among Medical Staff after One Year of the COVID-19 Pandemic.

(1) After one year of treating patients with SARS-CoV-2 infection, physical exhaustion is added to emotional stress and burnout syndrome. (2) By applying specific questionnaires, we evaluated healthcare workers who handled patients infected with SARS-CoV-2in terms of disease perception, perceived stress, emotional distress, and burnout syndrome after one year of the COVID-19 pandemic and compared them with staff who did not handle infected patients. (3) A total of 165 persons were evaluated, with 79 working in the COVID-19 department and 86 working in the non-COVID-19 department. No statistically significant differences were found in the perceived stress scores, emotional distress (functional or dysfunctional), and disease perception among the COVID-19 and non-COVID-19 groups. Also, we did not find any differences between the COVID-19 and non-COVID-19 departments concerning their total Maslach scores-50 in the COVID-19 department and 51 in the non-COVID-19 department, p = 0480-so a moderate level of burnout in the two groups. The only statistical difference was in the Maslach depersonalization scores, which were higher among COVID-19 workers (p = 0.024). (4) In our center, there was no statistically significant difference in perceived stress or emotional distress. The level of burnout syndrome seems to be the same among the two groups, regardless if they worked withCOVID-19-infected patients or not.

[The profile of serum inflammatory biomarkers in patients with SARS-CoV-2 infection: how well do they reflect the presence of pulmonary involvement?] / A gyulladásos biomarkerek profilja SARS-CoV-2-fertozésben szenvedo betegekben: mennyire tükrözik a tüdoérintettséget?

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory and imaging alterations that vary depending on the disease severity. OBJECTIVE: Monitoring changes in inflammatory biomarkers may offer insights into the extent of pulmonary alterations observed in chest-CT. This study aimed to evaluate the profile of different inflammatory biomarkers, widely available and routinely measured in COVID-19 patients, and to determine whether alterations in their activity at admission and discharge correlate with lung involvement assessed through CT scans. METHODS: We conducted a retrospective observational study, wherein chest-CT scans were performed upon admission, and blood tests were conducted at admission and discharge. Treatment and monitoring adhered to national and international guidelines. RESULTS: The profile of serum inflammatory markers (including values at admission and discharge, as well as their evolution during hospitalization) demonstrated a correlation with lung involvement as assessed by the total severity score. The high activity of serum inflammatory markers upon admission, accompanied by minimal changes during hospitalization, indicated a severe form of COVID-19 with notable lung involvement. While statistically significant differences were observed in C-reactive protein, fibrinogen, erythrocyte sedimentation rate, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio, C-reactive protein emerged as the most reliable marker for assessing pulmonary involvement. CONCLUSION: Changes in serum inflammatory markers during hospitalization exhibited a weak to moderate negative correlation with the severity of lung involvement. Orv Hetil. 2023; 164(41): 1607-1615.

Lung Microbiota in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis, and Unclassified Interstitial Lung Diseases: A Preliminary Pilot Study.

(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases.

Factors Associated with Prolonged RT-PCR SARS-CoV-2 Positive Testing in Patients with Mild and Moderate Forms of COVID-19: A Retrospective Study.

Background and objectives: This article aims to evaluate the number of days necessary for patients with mild and moderate forms of COVID-19 to reach undetectable levels of SARS-CoV-2 RNA in the upper respiratory tract specimens. As a secondary objective, we sought to establish a correlation between different conditions associated with longer viral load as this could result in a longer period of contagion and infectivity. Materials and Methods: It is a retrospective study. A total of 70 patients with confirmed mild and moderate forms of COVID-19 were enrolled in our study. Results: Number of days with traceable viral load was 25.93 (±6.02) days in patients with mild COVID-19 and 26.97 (±8.30) in moderate form (p = 0.72). Age, male gender, and obesity, along with several chronic conditions (cardiac, liver, renal, and neurological disease), were associated with prolonged positive RT-PCR test from the nasal swab (therefore prolonged viral load). These are in general, risk factors for severe forms of COVID-19. Conclusions: There are several conditions associated with prolonged positive RT-PCR in mild and moderate forms of COVID-19. As to why and what is the significance of it remains to be studied.

COPD in Firefighters: A Specific Event-Related Condition Rather than a Common Occupational Respiratory Disorder.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Smoking remains the most important risk factor, but occupational exposures may play an essential role as well. Firefighters are among occupations regularly exposed to a variety of irritative inhalational products, and they may be expected to develop respiratory health problems because of such an occupational exposure. To better understand and characterize this relationship, we performed an extensive search of the scientific literature, and we identified two major research areas: firefighters exposed to wildland fire smoke and firefighters involved in the World Trade Centre disaster-related operations. Most of the studies did not report a significant increase in COPD diagnosis in firefighters. An accelerated rate of decline in lung function was seen, a short time after major exposure events. This is the reason for an increased rate of exacerbations observed in individuals already diagnosed with obstructive respiratory disorders. A limited number of studies not covering these specific circumstances of exposure were found. They reported long-term morbidity and mortality data, and the results are controversial. Major confounding factors for most of the studies were the "healthy worker effect" and the lack of useful data regarding smoking habits. Efforts should be made in the future to better characterize specific biomarkers for the progression of COPD; to establish exposure limits; and to implement preventive strategies like rotation of workers, smoking cessation programs, and long-term monitoring programs for respiratory disorders.

Neutrophil-to-lymphocyte ratio, platelets-to-lymphocyte ratio, and eosinophils correlation with high-resolution computer tomography severity score in COVID-19 patients.

Inflammation has an important role in the progression of various viral pneumonia, including COVID-19. Circulating biomarkers that can evaluate inflammation and immune status are potentially useful in diagnosing and prognosis of COVID-19 patients. Even more so when they are a part of the routine evaluation, chest CT could have even higher diagnostic accuracy than RT-PCT alone in a suggestive clinical context. This study aims to evaluate the correlation between inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocytes ratio (PLR), and eosinophils with the severity of CT lesions in patients with COVID-19. The second objective was to seek a statically significant cut-off value for NLR and PLR that could suggest COVID-19. Correlation of both NLR and PLR with already established inflammatory markers such as CRP, ESR, and those specific for COVID-19 (ferritin, D-dimers, and eosinophils) were also evaluated. One hundred forty-nine patients with confirmed COVID-19 disease and 149 age-matched control were evaluated through blood tests, and COVID-19 patients had thorax CT performed. Both NLR and PLR correlated positive chest CT scan severity. Both NLR and PLR correlated positive chest CT scan severity. When NLR value is below 5.04, CT score is lower than 3 with a probability of 94%, while when NLR is higher than 5.04, the probability of severe CT changes is only 50%. For eosinophils, a value of 0.35% corresponds to chest CT severity of 2 (Se = 0.88, Sp = 0.43, AUC = 0.661, 95% CI (0.544; 0.779), p = 0.021. NLR and PLR had significantly higher values in COVID-19 patients. In our study a NLR = 2.90 and PLR = 186 have a good specificity (0.89, p = 0.001, respectively 0.92, p<0.001). Higher levels in NLR, PLR should prompt the clinician to prescribe a thorax CT as it could reveal important lesions that could influence the patient's future management.

Modification of exhaled air nitric oxide in patients with asthma - cortisone monotherapy or dual inhalation therapy?

INTRODUCTION: Asthma, a chronic lung disease, is a major health challenge worldwide with increased addressability to health services. There are different asthma phenotypes, which have different evolution and can be specifically tracked. The measurement of fractional expired nitric oxide (FeNo) with different devices reflects the eosinophilic inflammation of the airways, and can be used to evaluate the allergic phenotype and predict the treatment responses. The new GINA (Global Initiative for Asthma) guideline recommends FeNO monitoring to assess adherence to cortisone treatment in high doses before prescribing biological treatment, and as a means of monitoring the decrease in oral corticosteroid treatment. OBJECTIVE: The aim of the study is to analyze the applicability of FeNO in monitoring response to therapy. MATERIAL AND METHODS: An observational study was carried out on 129 subjects with a previously established diagnosis of asthma. The research was based on the determination of FeNO with NObreath. Those with intermediate FeNO received a low dose of inhaled corticosteroids in mono/dual therapy, those with increased FeNO received medium ICS mono/dual therapy. FeNO testing, its values and doses of ICS were below the the ATS / ERS guidelines. RESULTS: FeNO reduction is strictly dependent on the cortisone dose. Applying the dual therapy from the beginning does not bring additional benefits in comparison with cortisone in monotherapy, in terms of FeNO value. CONCLUSIONS: Recommendations that include FeNO testing can help monitor response to treatment.

Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in Various Respiratory Diseases: A Retrospective Analysis.

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) ratio are two extensively used inflammatory markers that have been proved very useful in evaluating inflammation in several diseases. The present article aimed to investigate if they have any value in distinguishing among various respiratory disorders. One hundred and forty-five patients with coronavirus disease 2019 (COVID-19), 219 patients with different chronic respiratory diseases (interstitial lung disease, obstructive sleep apnea(OSA)-chronic obstructive pulmonary disease (COPD) overlap syndrome, bronchiectasis) and 161 healthy individuals as a control group were included in the study. While neither NLR nor PLR had any power in differentiating between various diseases, PLR was found to be significant but poor as a diagnostic test when the control group was compared with the OSA-COPD group. NLR was found to be significant but poor as a diagnostic test when we compared the control group with all three groups (separately): the OSA-COPD group; interstitial lung disease group, and bronchiectasis group. NLR and PLR had poor power to discriminate between various respiratory diseases and cannot be used in making the differential diagnosis.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Neutrophil-To-Lymphocyte Ratio and Systemic Immune-Inflammation Index-Biomarkers in Interstitial Lung Disease.

Background and objectives: The aims of the study were to evaluate the utility of neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII) as inflammation markers and prognostic factors in patients with known interstitial lung disease secondary to connective tissue diseases (CTD-ILD) compared with idiopathic pulmonary fibrosis (IPF). Materials and Methods: Forty-two patients with known interstitial lung disease (21 with IPF and 21 with CTD-ILD) and 42 control matched healthy patients were included. The NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count, and the SII was calculated as follows: SII = platelets × neutrophils/lymphocytes, with the data being obtained from the patients data charts at admission, before any treatment. Results: our hypothesis was that in patients with interstitial lung disease NLR and SII would have higher values compared with patients with CTD-ILD or control healthy patients. The mean NLR value was 3.01 (±1.35) among patients with idiopathic pulmonary fibrosis, and 2.38 (±1.08) among patients with CTD-ILD without significant statistical difference (p = 0.92). There was however a clinically significant statistical difference when compared with the control group, where NLR was 2.00 (±1.05) (p = 0.003). SII values were 619.37 (±329.51) in patients with IPF, 671.55 (±365.73) in CTD-ILD group and 569.73 (±326.67) in healthy subjects (p = 0.13) Conclusions: A mean NLR value of 2.8 and a SII value over 500 in patients with connective diseases can become a marker of pulmonary interstitial involvement. In the context of non-exacerbated interstitial lung disease, NLR and SII have reduced numerical values, without being statistically correlated with prognosis when we compared with patients with connective tissue diseases without exacerbation or with healthy people, the cut off being of 2.4. However subsequent studies in larger patient samples might provide changes in these cut-off values.

Palliative Care Initiation in Chronic Obstructive Pulmonary Disease: Prognosis-Based, Symptoms-Based or Needs-Based?

The absence or late initiation of palliative care (PC) in chronic obstructive pulmonary disease (COPD) is multidimensional. To provide palliative care from the moment of COPD diagnosis remains utopic. Even the advanced forms or the end-of-life stages benefit late or never from these services. In this context, the research questions for the present systematic review were focused on the prognosis variables or multicomponent indices in COPD patients alongside the symptoms and unmet needs, which may be useful for the palliative care initiation. The aim was to help clinicians to identify not only the tools reliable to predict poor survival in COPD patients but also to identify the criteria for appropriateness for early palliative care onset. The search included systematic reviews and reviews published in English in the PUBMED database from Jan 1, 2015 to Jan 6, 2020. From a total of 202 findings, after applying filters, using additional sources, and eliminating duplicates, the search strategy screened 16 articles, out of which 10 were selected and included. A Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) flow diagram was constructed. The main domains identified as barriers in providing palliative care in COPD patients were complex: from the prognosis difficulties to the prognostic variables and scores proposed for initiating PC; from the troublesome symptoms or the unidimensional symptom tools to the unmet needs of COPD patients. The review concluded that none of the existing prognostic variables and multicomponent indices are reliable enough to exclusively predict poor survival in COPD patients and the decision to initiate PC should be rather based on the presence of refractory symptoms and patients' unmet needs and preferences. Despite the current advances, the ideal model to initiate palliative care from the moment COPD is diagnosed is a goal for clinicians trained in, and capable of providing palliative care in any COPD patient.

Disease Perception and Coping with Emotional Distress During COVID-19 Pandemic: A Survey Among Medical Staff.

The novel coronavirus disease, COVID-19, is a highly contagious infectious disease declared by the World Health Organization to be a pandemic and a global public health emergency. During outbreaks, health care workers are submitted to an enormous emotional burden as they must balance the fundamental "duty to treat" with their parallel duties to family and loved ones. The aims of our study were to evaluate disease perceptions, levels of stress, emotional distress, and coping strategies among medical staff (COVID-19 versus non-COVID-19 departments) in a tertiary pulmonology teaching hospital in the first month after the outbreak of COVID-19. One hundred and fifteen health care workers completed four validated questionnaires (the brief illness perception questionnaire, perceived stress scale, the profile of emotional distress emotional, and the cognitive coping evaluation questionnaire) that were afterwards interpreted by one psychologist. There was a high level of stress and psychological distress among health care workers in the first month after the pandemic outbreak. Interestingly, there were no differences between persons that worked in COVID-19 departments versus those working in non-COVID-19 departments. Disease perceptions and coping mechanisms were similar in the two groups. As coping mechanisms, refocusing on planning and positive reappraisal were used more than in the general population. There is no difference in disease perceptions, levels of stress, emotional distress, and coping strategies in medical staff handling COVID-19 patients versus those staff who were not handling COVID-19 patients in the first month after the pandemic outbreak.

Correlation between Transthoracic Lung Ultrasound Score and HRCT Features in Patients with Interstitial Lung Diseases.

Chest high-resolution computed tomography (HRCT) is considered the "gold" standard radiological method in interstitial lung disease (ILD) patients. The objectives of our study were to evaluate the correlation between two transthoracic lung ultrasound (LUS) scores (total number of B-lines score = the total sum of B-lines in 10 predefined scanning sites and total number of positive chest areas score = intercostal spaces with ≥3 B-lines) and the features in HRCT simplified scores, in different interstitial disorders, between LUS scores and symptoms, as well as between LUS scores and pulmonary function impairment. We have evaluated 58 consecutive patients diagnosed with ILD. We demonstrated that there was a good correlation between the total number of B-lines score and the HRCT simplified score (r = 0.784, p < 0.001), and also a good correlation between the total number of positive chest areas score and the HRCT score (r = 0.805, p < 0.005). The results confirmed the value of using LUS as a diagnostic tool for the assessment of ILD compared to HRCT. The use of LUS in ILD patients can be a useful, cheap, accessible and radiation-free investigation and can play a complementary role in the diagnosis and monitoring of these patients.

Fatal hypersensitivity pneumonitis after chemical occupational exposure.

Hypersensitivity pneumonitis (HP; extrinsic allergic alveolitis) is a rare non-immunoglobulin E (IgE)-mediated inflammatory lung disease caused by inhalation exposure (occupational, recreational or ordinary home exposure). A 36-year-old female patient, without significant medical history, is referred to an outpatient pulmonology clinic for dry cough, shortness of breath, fever, fatigue and weight loss. Chest high-resolution computed tomography (HRCT) was performed, and significant lung fibrosis (especially centrilobular and interlobular in bilateral "thick lines"), traction bronchiectasis and alveolitis in both superior lobes are described. Lung function tests showed severe restrictive dysfunction. Transfer factor of the lung for carbon monoxide (TLCO) being very low, the flexible bronchoscopy was contraindicated. Surgical lung biopsy was performed. Histopathological examination showed characteristic lesions of chronic bilateral hypersensitivity pneumonitis. The patient died four days after the surgical intervention due to post-operative complications. Exposure to various chemical substances can form bonds with human proteins molecules and induce an exaggerated immune response in susceptible individuals. A high index of suspicion of occupational exposure can determine an early diagnosis with a better outcome.