Acrometastasis due to lung adenocarcinoma

We are presenting a case of acrometastasis in a male patient with lung adenocarcinoma. Acrometastases accumulate for 0.1%of all metastatic bone lesions and can be the first manifestation of cancer in approximately 10% of cases. The main clinicalmanifestations are tenderness, intermittent pain, functional impairment, erythema, heat and swelling of the affected part. Lungcancer is the main primary malignancy which causes acrometastases. Although the lesions can be recognized in x-rays or CTscans, the gold standard for the diagnosis is MRI scan in which the full extension of the tumor can be evaluated.The diagnosisis usually confirmed by fine-needle biopsy of the affected bone. In the presence of acrometastases, prognosis is very poor andpalliative treatment is usually recommended. This case shows that patients at risk for lung cancer should be screened intensivelywhen they develop persistent digital symptoms

Airway inflammation in obstructive sleep apnea: Is leptin the missing link?

SummaryBackgroundLocal and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements.Patients & MethodsAbout 45 OSA patients (mean AHI 40±25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-α and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed.ResultsAn increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements.ConclusionsIncreased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity

Przerzuty gruczolakoraka płuca do kości dystalnych części kończyn

W pracy przedstawiono przypadek mężczyzny z przerzutami gruczolakoraka płuca do kości dystalnych części kończyn. Przerzuty do kości dystalnych części kończyn stanowią 0,1% wszystkich kostnych zmian przerzutowych, a w około 10% przypadków mogą być pierwszą manifestacją raka. Głównymi objawami klinicznymi są: tkliwość uciskowa, ból przerywany, upośledzenie czynnościowe, rumień, wzmożone ucieplenie oraz obrzęk zajętej części kończyny. Rak płuca jest głównym pierwotnym nowotworem złośliwym dającym przerzuty do kości dystalnych części kończyn. Mimo że zmiany te mogą być wykryte na radiogramach lub w tomografii komputerowej, „złotym standardem” diagnostyki pozostaje badanie rezonansem magnetycznym, w którym można ocenić pełny zakres zmian. Rozpoznanie jest zwykle potwierdzane za pomocą biopsji cienkoigłowej zajętej kości. W przypadku obecności przerzutów do kości dystalnych części kończyn rokowanie jest niekorzystne i zwykle stosuje się leczenie paliatywne. Przedstawiony przypadek pokazuje, że u pacjentów ze zwiększonym ryzykiem raka płuca, z nieustępującymi objawami ze strony palców, należy przeprowadzić szeroką diagnostykę.W pracy przedstawiono przypadek mężczyzny z przerzutami gruczolakoraka płuca do kości dystalnych części kończyn. Przerzuty do kości dystalnych części kończyn stanowią 0,1% wszystkich kostnych zmian przerzutowych, a w około 10% przypadków mogą być pierwszą manifestacją raka. Głównymi objawami klinicznymi są: tkliwość uciskowa, ból przerywany, upośledzenie czynnościowe, rumień, wzmożone ucieplenie oraz obrzęk zajętej części kończyny. Rak płuca jest głównym pierwotnym nowotworem złośliwym dającym przerzuty do kości dystalnych części kończyn. Mimo że zmiany te mogą być wykryte na radiogramach lub w tomografii komputerowej, „złotym standardem” diagnostyki pozostaje badanie rezonansem magnetycznym, w którym można ocenić pełny zakres zmian. Rozpoznanie jest zwykle potwierdzane za pomocą biopsji cienkoigłowej zajętej kości. W przypadku obecności przerzutów do kości dystalnych części kończyn rokowanie jest niekorzystne i zwykle stosuje się leczenie paliatywne. Przedstawiony przypadek pokazuje, że u pacjentów ze zwiększonym ryzykiem raka płuca, z nieustępującymi objawami ze strony palców, należy przeprowadzić szeroką diagnostykę

New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis

Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) or without (CRSsNP) are chronic respiratory diseases. These two disorders often co-exist based on common anatomical, immunological, histopathological, and pathophysiological basis. Usually, asthma with comorbid CRSwNP is driven by type 2 (T2) inflammation which predisposes to more severe, often intractable, disease. In the past two decades, innovative technologies and detection techniques in combination with newly introduced targeted therapies helped shape our understanding of the immunological pathways underlying inflammatory airway diseases and to further identify several distinct clinical and inflammatory subsets to enhance the development of more effective personalized treatments. Presently, a number of targeted biologics has shown clinical efficacy in patients with refractory T2 airway inflammation, including anti-IgE (omalizumab), anti-IL-5 (mepolizumab, reslizumab)/anti-IL5R (benralizumab), anti-IL-4R-α (anti-IL-4/IL-13, dupilumab), and anti-TSLP (tezepelumab). In non-type-2 endotypes, no targeted biologics have consistently shown clinical efficacy so far. Presently, multiple therapeutical targets are being explored including cytokines, membrane molecules and intracellular signalling pathways to further expand current treatment options for severe asthma with and without comorbid CRSwNP. In this review, we discuss existing biologics, those under development and share some views on new horizons.</p

Vascular endothelial growth factor and cysteinyl leukotrienes in sputum supernatant of patients with asthma

SummaryBackgroundVascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor in asthma. Cysteinyl leukotrienes (Cyst-LTs) have been implicated in vascular permeability in asthma. Cyst-LTs receptor antagonists modulate vascular permeability by reducing VEGF expression.ObjectiveWe aimed to determine the levels of VEGF and Cyst-LTs in sputum supernatants of patients with asthma and to investigate possible associations within them and with airway vascular permeability (AVP) index. Possible confounding factors were also assessed.MethodsOne hundred twenty one patients with asthma (38 with severe refractory asthma, 41 smokers) and 30 healthy subjects (15 smokers) were studied. All subjects underwent lung function tests, and sputum induction for cell count identification and VEGF, Cyst-LTs, measurement in supernatants. AVP index was also assessed.ResultsBoth VEGF & Cyst-LTs (pg/ml) levels were significantly elevated in patients with asthma compared to normal subjects (median, interquartile ranges 845 [487–1034] vs. 432 (327–654) and 209 [171–296] vs. 92 [75–114] respectively, p < 0.001 for both). Multivariate regression analysis in the whole group showed a significant association of Cyst-LTs levels in sputum supernatants with VEGF levels in sputum supernatants and AVP index. A similar positive association was observed between VEGF levels in sputum supernatants and AVP index. The presence of Severe asthma was a significant covariate for both associations.ConclusionOur results indicate that Cyst-LTs may modulate vascular permeability by up-regulating VEGF expression. The above effect seems to be affected by asthma severity

Physiological predictors of peak inspiRatory flow using Observed lung function results (POROS) : evaluation at discharge among patients hospitalized for a COPD exacerbation

This study was supported by AstraZeneca. The abstract of this paper was presented at the American Thoracic Society International Conference 2017 as a poster presentation with interim findings.Peer reviewedPublisher PD

Serum Levels of Surfactant Proteins in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE)

Introduction Emphysema and idiopathic pulmonary fibrosis (IPF) present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE). Serum surfactant proteins (SPs) A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival. Methods 122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE) and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year. Results SP-A and SP-D levels differed between groups (p = 0.006 and p= 26 ng/mL) presented a weak association with reduced survival (p = 0.05). Conclusion In conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials

Airway inflammation in obstructive sleep apnea: Is leptin the missing link?

SummaryBackgroundLocal and systemic inflammation is implicated in the pathophysiology of Obstructive Sleep Apnea (OSA). Exhaled breath condensate (EBC) is a non-invasive sampling method for the lower airways. However, it is important to consider the potential effect of the systemic origin whereas systemic inflammation is significantly elevated. This prospective study was designed to investigate whether airway inflammation is significantly related to plasma leptin levels in OSA patients. Simultaneously, it was designed to investigate whether inflammatory variables predict parameters expressing disease severity and finally whether smoking habit affect the above measurements.Patients & MethodsAbout 45 OSA patients (mean AHI 40±25, 28 smokers) and 25 healthy controls (AHI<5, 15 smokers) were studied and underwent overnight diagnostic polysomnography. We measured pH, 8-isoprostane, TNF-α and IL-6 in EBC and leptin in plasma. Plausible associations between leptin and inflammatory parameters were analyzed after adjustment for proper variables. Similar associations between inflammatory variables and parameters of disease severity were also performed.ResultsAn increased level of leptin and respective increase of inflammatory variables was found. No significant association was observed between parameters of EBC and plasma leptin levels. A part of the parameters of disease severity is significantly associated with pH and 8-isoprostane. Smoking did not seem to be a critical confounding factor for evaluation of the above measurements.ConclusionsIncreased levels of leptin were not associated with the observed airway inflammation in OSA. The observed airway inflammation seemed to be independent of smoking habit with limited association with disease severity

Phenotyping and Endotyping Asthma Based on Biomarkers

Asthma is a chronic inflammatory airways disorder mainly characterized by heterogeneity. A phenotype is defined as a group of patients that present similar clinically observable characteristics, without establishing a direct etiologic relationship with a distinct pathophysiologic mechanism. An endotype, on the other hand, describes a subgroup that shares the same pathophysiologic processes that lead to the development, the progression and the presentation of a disease. A biomarker has been defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention. Several inflammatory phenotypes have been identified by the use of biomarkers. Most of them are based on the predominant type of cells in different biological fluids with sputum to be remained the most representative one. Eosinophilia represents the major characteristic of what we called classic atopic asthma. This particular phenotype usually responds well to corticosteroids, except for a small subgroup of severe asthma where even in the presence of eosinophils the ICS seem to have a less responsive role. Neutrophilic phenotype driven by the presence of neutrophils shows inadequate response to corticosteroid treatment, even in mild asthma. The major approach in order to define an endotype is driven by three main parameters. The statistical clustering approach, the use of advanced statistical mathematics to create distinct patient clusters, the specific targeted immune therapies and finally the application of omics&apos; approach. Both phenotypes and endotypes are trying to clarify mechanisms and processes that driven the complexity of asthma. Both concepts could identify approaches which could establish new targeted to specific biomarkers treatment therapies/strategies

Oxidative Stress in Patients with COPD

The lung is the organ with the highest exposure to ambient air in the entire human architecture. Due to its large surface area and blood supply, the lung is susceptible to oxidative injury in the form of myriads of reactive oxygen species (ROS) and free radicals. In order to provide defense against the oxidative burden, the lungs produce various endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/ROS, either of endogenous or environmental origin. Several mechanisms are related to the potential connection between COPD and oxidative stress. One of the most important actions of the oxidative stress is the influence of the molecular mechanisms involved in the expression proinflammatory genes. There is plenty of evidence supporting an imbalance between oxidants and antioxidants in the lung and systemic circulation of smokers and COPD patients. Detection of the oxidative burden and evaluation of their progression and phenotypes by oxidative stress biomarkers have proven challenging and difficult. Both invasive and non-invasive techniques have provided different biomarkers which contribute to the oxidative burden of the airways. An effective wide-spectrum antioxidant therapy with bioavailability is urgently needed to control the local and systemic oxidative burst in COPD. In that direction, several antioxidant agents have been evaluated as potential candidates for the management of COPD. However, despite some encouraging results, clinical trials so far have failed to elaborately define the type of antioxidant, the regimen and the time period of treatment that may improve clinically meaningful outcomes in patients with COPD