The most common cause of death in patients with amyotrophic lateral sclerosis (ALS) is respiratory failure, often in the period of 2-5 years, with a small percentage of patients surviving up to 10 ...years or more. The aim of the study was to evaluate the significance of pulmonary function tests in prediction of mortality and definition of indications for noninvasive mechanical ventilation (NIMV).
This retrospective-prospective study was performed at the Clinic of Pulmonology, Clinical Centre of Serbia in the period from January 2015 to December 2017. Patients with diagnosis of ALS established according to El Escorial criteria were included.
The study included 76 patients with ALS, 50 (65.85%) with spinal and 26 (34.2%) with bulbar form of disease. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV
) were higher in spinal form of ALS, and the difference was statistically significant when compared to bulbar form. Form of disease, FVC < 70%, maximum inspiratory pressure (PI
) < 50 and maximum expiratory pressure (PE
) < 50 were significant factors for survival. The patients with bulbar form of disease had 2.174 (95.0% CI: 1.261-3.747) higher risk for death.
Our study points to the significance of timely application and early start of NIMV in patients with ALS as an important approach to defer functional impairment, which would mean that the criteria, in our country, for application of these devices must be changed, not only regarding the value of current functional diagnostic tests used in everyday practice in patients with ALS but also in regard to the introduction of new diagnostic tests, such as sniff nasal inspiratory pressure and/or polysomnographic testing.
Lung cancer is among leading causes of death worldwide. Different histological types of the lung carcinoma show significant differences in behavior.
The aim of this study is to determine the ...distribution patterns of metastases of different lung cancer histological types in autopsied individuals.
Protocols from all autopsies performed at the Institute of Pathology from 2008 till 2014 were reviewed retrospectively, and information on individuals' age, sex, histological type of primary lung cancer, presence and location of metastases, and causes of death were recorded.
More than 90% of the individuals with lung cancer metastases were older than 50 years (mean age: 64.5 ± 10.3), with two-fold male predominance. The most frequent histological type in both sexes was adenocarcinoma (48%). Although, in general, hematogenous metastases were mostly found in the liver and adrenal glands, various histological types of lung cancer show specific dissemination patterns. Metastases in adrenal glands derived mostly from adenocarcinoma and large-cell carcinoma. Metastases in the intestines most frequently originated from large-cell carcinoma (
= 0.01). Metastatic complications and bronchopneumonia were the most frequent causes of death.
While, overall, the most frequent hematogenous metastases occur in the liver and adrenal glands, various histological types of lung cancer show specific dissemination patterns. Knowing distribution of metastases is essential for making algorithms of treatment, as well as for improving clinical assessment of the patients with unclear clinical findings and suspicion on occult primary lung cancer.
Introduction
Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask ...effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England–King’s Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment.
Objective
The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated.
Methods
A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ ‐ new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale–MRC, Borg Dyspnea Scale and 15D as general questionnaire.
Results
KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.
Bronchiectasis is a chronic progressive respiratory disease characterized by permanent dilatation of the bronchi. It is a complex condition with numerous different etiologies, co-morbidities, and a ...heterogeneous presentation. As we know, there is a lack of studies that describe the differences and compare the characteristics between focal and multifocal bronchiectasis. The aim of this study is to identify differences in clinical characteristics presentation, severity or distribution in focal and multifocal bronchiectasis, and prognostic implications.
126 patients with computed tomography (CT)-verified bronchiectasis were enrolled. Baseline characteristics that included age, sex, smoking history, and respiratory symptoms were recorded, with special attention paid to hemoptysis appearance, body mass index, and comorbidities. The type of bronchiectasis determined by CT scan and the modified Reiff scores indicating radiological severity were recorded. Patients were divided in two groups (I is focal and II is multifocal).
There were no statistically significant differences in age, smoking status, comorbidity, and BMI between the two groups. Multifocality was associated with a significantly higher proportion of females (
= 0.014), the rate of hemoptysis (
= 0.023), and the number of hospitalizations, but not of exacerbations and prevalence of immunodeficiency (
= 0.049). Significantly, a high number of subjects with multifocality had bronchiectasis of moderate severity, and post-infective and asthma-associated phenotypes were the dominant in this group. Unexpectedly, the cystic and varicose radiological phenotype (which need more time to develop) were more dominant in the focal group. The cylindrical phenotype was equally observed in the multifocal and focal groups.
Our study suggests that multifocality is not related to age, number of exacerbations, or radiological phenotype, but it seems to be associated with the clinical post-infective phenotype, immunodeficiency, frequent hospitalizations, and severity. Thus, the presence of multifocal bronchiectasis may act as a biomarker of severity and poor outcomes in these patients.
Cutaneous manifestations due to drugs used in the treatment of gastrointestinal disorders are multiple and common. Adequate diagnosis is of great importance, bearing in mind that the therapeutic ...regimen depends on its diagnosis. In this review, we provided an overview of the most common drug-induced skin lesions with a detailed explanation of the disease course, presentation and treatment, having in mind that in recent years, novel therapeutic modalities have been introduced in the treatment of various gastrointestinal disorders, and that incidence of cutaneous adverse reactions has been on the rise.
Background
Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with ...pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19.
Methods
Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity.
Results
Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (
p
= 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (
p
< 0.0001). Serum concentrations of IgG (
p
= 0.003) and IgA (
p
= 0.032) were significantly lower in this group of patients. Higher total serum IgA (
p
= 0.009) was associated with mortality, with no difference in serum IgG (
p
= 0.115) or IgM (
p
= 0.175). Lethal outcome was associated with lower complement C4 (
p
= 0.013), while there was no difference in complement C3 concentration (
p
= 0.135).
Conclusion
Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.
Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the ...pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (
n
= 80) against patients without pneumonia (
n
= 48), and (2) severe (
n
= 34) against mild disease (
n
= 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene
KLHL1
(
p
= 1.91 × 10
−8
). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in
SACM1L
and
LZTFL1
genes suggestively associated with pneumonia (
p
= 7.54 × 10
−6
) and severe COVID-19 (
p
= 6.88 × 10
−7
), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (
IRX, NDUFS6, MRPL36, p
= 2.81 × 10
−6
), 5q11.2 (
ESM1, p
= 6.59 × 10
−6
), and 9p23 (
TYRP1, LURAP1L
,
p
= 8.69 × 10
−6
). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
Inflammation, oxidative stress and an imbalance between proteases and protease inhibitors are recognized pathophysiological features of chronic obstructive pulmonary disease (COPD). The aim of this ...study was to evaluate serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with COPD and to assess their relationship with lung function, symptom severity scores and recent acute exacerbations.
In this observational cohort study, serum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 ratio in the peripheral blood of COPD patients with stable disease and healthy controls were determined, and their association with lung function (postbronchodilator spirometry, body plethysmography, single breath diffusion capacity for carbon monoxide), symptom severity scores (mMRC and CAT) and exacerbation history were assessed.
COPD patients (n = 98) had significantly higher levels of serum MMP-9 and TIMP-1 and a higher MMP-9/TIMP-1 ratio than healthy controls (n = 47) (p ≤ 0.001). The areas under the receiver operating characteristic curve for MMP-9, TIMP-1 and the MMP-9/TIMP-1 ratio for COPD diagnosis were 0.974, 0.961 and 0.910, respectively (all p < 0.05). MMP-9 and the MMP-9/TIMP-1 ratio were both negatively correlated with FVC, FEV
FEV
/FVC, VC, and IC (all p < 0.05). For MMP-9, a positive correlation was found with RV/TLC% (p = 0.005), and a positive correlation was found for the MMP-9/TIMP-1 ratio with RV% and RV/TLC% (p = 0.013 and 0.002, respectively). Patients with COPD GOLD 3 and 4 presented greater MMP-9 levels and a greater MMP-9/TIMP-1 ratio compared to GOLD 1 and 2 patients (p ≤ 0.001). No correlation between diffusion capacity for carbon monoxide and number of acute exacerbations in the previous year was found.
COPD patients have elevated serum levels of MMP-9 and TIMP-1 and MMP-9/TIMP-1 ratio. COPD patients have an imbalance between MMP-9 and TIMP-1 in favor of a pro-proteolytic environment, which overall indicates the importance of the MMP-9/TIMP-1 ratio as a potential biomarker for COPD diagnosis and severity.
In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients.
The prospective clinical study included 46 ...patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO
, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot.
On discharge, in comparison with admission, the values of SpO
were significantly lower (
= 0.007) before the 6MWT, and VAS scores were significantly higher (
= 0.036), while after the 6MWT, VAS scores were significantly lower (
< 0.001) as were Borg scores (
= 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (
= 0.005) before the StS test, and Borg scores were significantly lower (
= 0.001), while after the StS test, SpO
levels were significantly higher (
= 0.036) and VAS scores were significantly lower (
< 0.001), as were Borg scores (
= 0.008). After discharge, the values of the StS test were significantly higher (
= 0.011), PHQ9 scores were significantly lower (
< 0.001) and GAD anxiety scores were significantly lower as well (
= 0.005), while the distances measured in meters on the 6MWT were significantly increased (
< 0.001).
A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.
Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40–50%. The disease is characterized by ...slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient’s condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA.
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