The growth of non-solid neoplastic lung nodules is associated with low PD L1 expression, irrespective of sampling technique.

BACKGROUND: Few data are known regarding the molecular features and patterns of growth and presentation which characterize those lung neoplastic lesions presenting as non-solid nodules (NSN). METHODS: We retrospectively reviewed two different cohorts of NSNs detected by CT scan which, after transthoracic fine-needle aspiration (FNA) and core needle biopsy (CNB) received a final diagnosis of malignancy. All the enrolled patients were then addressed to surgical removal of lung cancer nodules or to exclusive radiotherapy. Exhaustive clinical and radiological features were available for each case. RESULTS: In all 62 analysed cases the diagnosis of adenocarcinoma (ADC) was reached. In cytologic samples, EGFR activating mutations were identified in 2 of the 28 cases (7%); no case showed ALK/EML4 or ROS1 translocations. In the histologic samples EGFR activating mutation were found in 4 out of 25 cases (16%). PD-L1 immunostains could be evaluated in 30 cytologic samples, while the remaining 7 did not reach the cellularity threshold for evaluation. TPS was < 1% in 26 cases, > 1% < 50% in 3, and > 50% in 1. All surgical samples showed TPS < 1%. Of the 17 cases that could be evaluated on both samples, 15 were concordantly TPS 0, and 2 showed TPS > 1% < 50 on the biopsy samples. TPS was < 1% in 14 cases, > 1%/< 5% in 4 cases, > 5%/< 50% in 2 cases, > 50% in 1 case. CONCLUSIONS: Overall PD-L1 immunostaining documented the predominance of low/negative TPS, with high concordance in FNA and corresponding surgical samples. It can be hypothesized that lung ADC with NSN pattern and predominant in situ (i.e. lepidic) components represent the first steps in tumor progression, which have not yet triggered immune response, and/or have not accumulated a significant rate of mutations and neoantigen production, or that they belong to the infiltrated-excluded category of tumors. The negative prediction of response to immunomodulating therapy underlines the importance of rapid surgical treatment of these lesions. Notably, cell block cytology seems to fail in detecting EGFR mutations, thus suggesting that this kind of sampling technique should be not adequate in case of DNA direct sequencing.

Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients.

BACKGROUND: Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD. METHODS: Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year. RESULTS: Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02]. The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001). CONCLUSIONS: In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D. This association was independent of patients' characteristics and comorbidities.

Laryngeal spasm mimicking asthma and vitamin d deficiency.

We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respiratory clinic for suspect bronchial asthma. Spirometry showed mild decrease in inspiratory flows. Methacholine challenge was negative. Dyspnea was triggered by hyperventilation-induced hypocapnia, which produced marked decrease in airflow rates, particularly in inspiratory flows, consistent with laryngospasm. Nutritional assessment of the patient showed low serum level of calcium and vitamin D, attributable to avoidance of milk and dairy products for lactose intolerance and to insufficient sunlight exposure. After calcium and vitamin D supplementation episodic laryngospasm disappeared and hypocapnic hyperventilation test induced very mild change in airflow rates. Calcium and vitamin D deficiency may favour laryngeal spasm mimicking asthma, particularly in subjects with underlying myopathy.

Predictors of cardiovascular disease in asthma and chronic obstructive pulmonary disease.

BACKGROUND: Cardiovascular disease (CVD) is a common comorbidity in patients with chronic airway obstruction, and is associated with systemic inflammation and airway obstruction. The aim of this study was to evaluate the predictors of CVD in two different conditions causing chronic airway obstruction, asthma and COPD. METHODS: Lung function tests, clinical and echocardiographic data were assessed in 229 consecutive patients, 100 with asthma and 129 with COPD. CVD was classified into: pressure overload (PO) and volume overload (VO). Sub-analysis of patients with ischemic heart disease (IHD) and pulmonary hypertension (PH) was also performed. RESULTS: CVD was found in 185 patients (81%: 51% COPD and 30% asthmatics) and consisted of PO in 42% and of VO in 38% patients. COPD patients, as compared to asthmatics, had older age, more severe airway obstruction, higher prevalence of males, of smokers, and of CVD (91% vs 68%), either PO (46% vs 38%) or VO (45% vs 30%). CVD was associated with older age and more severe airway obstruction both in asthma and COPD. In the overall patients the predictive factors of CVD were age, COPD, and male sex; those of PO were COPD, BMI, VC, FEV1 and MEF50 and those of VO were age, VC and MEF50. In asthma, the predictors of CVD were VC, FEV1, FEV1 /VC%, and PaO2, those of PO were VC, FEV1 and FEV1 /VC%, while for VO there was no predictor. In COPD the predictors of CVD were age, GOLD class and sex, those of VO age, VC and MEF50, and that of PO was BMI. Sub-analysis showed that IHD was predicted by COPD, age, BMI and FEV1, while PH (found only in 25 COPD patients), was predicted by VO (present in 80% of the patients) and FEV1. In subjects aged 65 years or more the prevalence of CVD, PO and VO was similar in asthmatic and COPD patients, but COPD patients had higher prevalence of males, smokers, IHD, PH, lower FEV1 and higher CRP. CONCLUSIONS: The results of this study indicate that cardiovascular diseases are frequent in patients with chronic obstructive disorders, particularly in COPD patients. The strongest predictors of CVD are age and airway obstruction. COPD patients have higher prevalence of ischemic heart disease and pulmonary hypertension. In the elderly the prevalence of PO and VO in asthma and COPD patients is similar.