Use of Remdesivir in Patients Hospitalized for COVID-19 Pneumonia: Effect on the Hypoxic and Inflammatory State.

Remdesivir is one of the most attractive options for patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). The aim of our study was to evaluate the effect of remdesivir on the hypoxic and inflammatory state in patients with moderate to severe COVID-19. We retrospectively enrolled 112 patients admitted for COVID-19 pneumonia, requiring low-flow oxygen, 57 treated with remdesivir plus standard of care (SoC) and 55 treated only with SoC that were similar for demographic and clinical data. We evaluated changes in hypoxemia and inflammatory markers at admission (Day 0) and after 5 days of treatment (Day 5) and the clinical course of the disease. From Day 0 to Day 5, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) increased from 222 ± 62 to 274 ± 97 (p < 0.0001) in the remdesivir group and decreased from 223 ± 62 to 183 ± 76 (p < 0.05) in the SoC group. Interleukine-6 levels decreased in the remdesivir (45.9 to 17.5 pg/mL, p < 0.05) but not in the SoC group. Remdesivir reduced the need for ventilatory support and the length of hospitalization. In conclusion, compared to standard care, remdesivir rapidly improves hypoxia and inflammation, causing a better course of the disease in moderate to severe COVID-19.

Female Sex Affects Respiratory Function and Exercise Ability in Patients Recovered from COVID-19 Pneumonia.

Background: Coronavirus-19 Disease (COVID-19) may cause persistent symptoms and functional respiratory impairment, known as long COVID. Determinants of long COVID are unclear. Although males experience more severe acute illness, the impact of sex on the occurrence of long-term sequelae is unknown. The aim of this study was to establish whether sex affects pulmonary function, exercise capacity, and clinical outcomes in patients recovered from COVID-19 pneumonia. Materials and Methods: We performed a retrospective analysis on patients evaluated in our "Post-COVID Clinic" after a median follow-up of 128 days from the acute disease. Tests performed included standard spirometry, diffusion capacity of the lung for carbon monoxide (DLCO), and 6-minute walk test (6-MWT). Results: A total of 157 patients (mean age 59.9 ± 12, 91 males) recovered from mild to severe pneumonia, without previous respiratory disease, were included. No differences in demographic data and in the severity of the acute illness were observed between the two study groups, males and females. Abnormal alveolar diffusion was more common and severe among females (DLCO <80% in 31% of males vs. 53% of females, p < 0.01; DLCO <70%, in 20% of males vs. 40% of females, p < 0.01). Severe reduction in 6-MWT was observed in 20% of males versus 46% of females (p < 0.01). Multiple logistic regression showed that female sex was an independent predictor of abnormal DLCO and 6-MWT. The prevalence of symptoms and radiological abnormalities was similar in the two groups. Conclusions: These data show that at 4 months follow-up women recovered from COVID-19 pneumonia are more likely to exhibit a reduced alveolar diffusion capacity and exercise tolerance than men, although a similar severity of the acute disease.

Contribution of pulmonary function tests (PFTs) to the diagnosis and follow up of connective tissue diseases.

INTRODUCTION: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. MAIN BODY: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DLCO appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. CONCLUSIONS: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease.

Blastoschizomyces capitatus pneumonia in a patient with untreated chronic lymphocytic leukemia.

Several cases have been reported of B. capitatus infections in immunocompromised patients. Acute leukemia is the main predisposing factor. Chronic lymphocytic leukemia (CLL) is not usually associated with opportunistic infections. We report a case of pulmonary infection by B. capitatus in a patient with untreated chronic lymphocytic leukemia. Although the patient had a complete recovery, we believe that this report will alert clinicians to consider B. capitatus as possible cause of severe pneumonia in untreated CLL.

Exhaled markers of antioxidant activity and oxidative stress in stable cystic fibrosis patients with moderate lung disease.

The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/antioxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F2α (8-isoprostane), a marker of oxidative stress, in the exhaled breath condensate of 17 non-smoking patients with CF, in stable phase, and in 17 age-matched healthy subjects. The levels of GSH and total antioxidant capacity in patients with CF were significantly lower than in healthy subjects (0.66 ± 0.07 µM versus 1.30 ± 0.08 µM, p < 0.001, respectively for GSH; 0.157 ± 0.02 mM and 0.32 ± 0.01 mM, p < 0.05, respectively for antioxidant capacity). The concentration of 8-isoprostane was higher in CF than in healthy controls (26.5 ± 0.1 pg ml-1 versus 10.8 ± 0.1 pg ml-1; p < 0.05). A low concentration of antioxidant agents, particularly glutathione, and increased levels of 8-isoprostane in the exhaled breath suggest an altered oxidizing environment in the airways of patients with CF. This altered redox environment in the epithelial liquid surface may contribute to progressive lung disease.

Most Italians attending a congress on health of elderly people do not know and do not recognize respiratory diseases.

BACKGROUND: The present study reports the results of a survey jointly carried out by three Italian respiratory scientific associations (AIMAR, AIPO, SIMeR) together with an important Federation of elderly patients (FederAnziani) during the National Conference of Italian Court for Health Right held in Rimini from November 29(th) to December 1(st), 2013. The survey, based on a spirometric examination preceded by a questionnaire on respiratory health, was conducted on elderly people coming from all Italian regions to attend the Conference. METHODS: Nine hundred forty-nine subjects (574 females and 375 males), mean age 66.2 ± 10.1 years, were interviewed and performed spirometric examination. There were 137 smokers (14.4 %). Mean value of Body Mass Index (BMI) was significantly higher in males (27.6 ± 6.6) than in females (26.3 ± 4.3). RESULTS: 17.1 % (N = 143) of the studied subjects reported to be suffering from respiratory disease and the prevalent illnesses were asthma (31.5 %) and COPD/emphysema (24.5 %), but only 3.3 % of the whole surveyed group was able to identify COPD as a pulmonary disease, however without knowing its characteristics, while these were known by 0.5 % of the interviewed subjects only. A high number of subjects, 22 % of whom were smokers, declared chronic sputum production. 10.2 % of the study group showed an obstructive defect at spirometry when the criterium of lower limit of the normal (LLN) was considered, whereas it was 12.4 % if the fixed limit of 0.70 was chosen. 64 % of the obstructed people thought they did not have any respiratory disease. CONCLUSIONS: The results of this survey, able to spread the knowledge of respiratory diseases and spirometry in a wide sample of subjects for the most part scarcely aware of them, emphasize the need for a greater divulgation of respiratory issues among the general population.

Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.

Cytoreductive surgery and hyperthermic intraoperative intrapleural chemotherapy (HITHOC) are a known option for malignant pleural mesothelioma (MPM). This prospective study was started to prove that pleurectomy/decortication and HITHOC could be successfully performed in a low volume center. Criteria of inclusion were a proven diagnosis of MPM, early-stage disease and good performance status. Six consecutive patients were enrolled. After pleurectomy/decortication, intrapleural cisplatin was administered for 60 min at 42.5 °C. Wedge resections and diaphragmatic reconstruction were added in two and one patient, respectively. Morbidity was 16.6%. Mortality was nil. Hospital stay was 7.8 days. Mean survival was 21.5 months (range: 6-30). This small experience confirms that pleurectomy/decortication and HITHOC are a good therapeutic option in the multimodality treatment of MPM. A randomized controlled trial is necessary.

Kartagener's syndrome: review of a case series.

BACKGROUND: Kartagener Syndrome (KS) is a rare autosomal recessive genetic disorder, resulting in a group of clinical manifestations, including bronchiectasis, chronic pansinusitis and situs inversus. METHODS: We hereby reviewed eight cases of this rare entity selected from patients attending our outpatients Respiratory Unit since 2006. Samples of respiratory epithelium were obtained with the method of nasal brushing and sent to a specialized center in order to be studied with electron microscopy. At least 50 cross sections of different cilia from different cells were observed in each specimen to study the axonemal structure. Electron micrographs were taken at a magnification of X 50,000 to determine the orientation of the cilia and at a magnification of X 110,000 to study the axonemal pattern. The incidence of abnormal cilia was expressed as a percentage. RESULTS: We observed different ultrastructural defects in our KS patients, including absence of outer dynein arms, absence of outer and inner dynein arms, and absence of the central pair with transposition of a peripheral doublet into the central position. Patient's follow up lasted till 2014, however two patients with more severe clinical behavior died before. CONCLUSIONS: This is a review of a case series, yet our data has shown that nasal brushing with ultrastructural pathological differentiation may be useful to identify patients with high risk and to develop more complex clinical presentations.

Wider implications of video-assisted thoracic surgery versus open approach for lung metastasectomy.

Lung metastasectomy is considered a safe and potentially curative procedure despite there is not a strong evidence that metastasectomy prolongs long-term survival in patients with lung metastases. Moreover, the debate is open regarding the best approach for lung metastasectomy, video-assisted thoracic surgery versus open approach. A systematic review of literature to clarify what is the best approach to prolong survival in patients with lung metastases was performed. Our study confirms that overall survival is equivalent for video-assisted thoracic surgery and thoracotomy, therefore the 'gold standard' surgical treatment for lung metastases remains a point of debate. The choice of the surgical approach still depends more on the single center or surgeon practice than on strong scientific evidence. A prospective randomized trial could clarify the question.

Cytoreductive surgery and hyperthermic intrapleural chemotherapy for malignant pleural diseases: preliminary experience.

Cytoreductive surgery and hyperthermic-intraoperative-intrapleural-chemotherapy (HITHOC) is a known approach for malignant pleural diseases (MPD). This study was started to clarify the role of cytoreductive surgery and HITHOC in MPD. Criteria of inclusion were early-stage disease in malignant pleural mesothelioma (MPM), young age, good condition and selected stage-M1a lung cancer. Six patients with MPM and two patients with lung cancer were enrolled. After surgical debulking, intrapleural cisplatin was administered for 60 min at 42.5°C. Wedge, rib resection and repaired diaphragm were added in three, one and one patient, respectively. Morbidity, toxicity and mortality was nil. Hospital stay was 8 days. Mean survival is 13.6 months. This experience confirms that cytoreductive surgery and HITHOC is a good option in the treatment of MPD. A randomized controlled trial is necessary.

A retrospective study on acute health effects due to volcanic ash exposure during the eruption of Mount Etna (Sicily) in 2002.

BACKGROUND: Mount Etna, located in the eastern part of Sicily (Italy), is the highest and most active volcano in Europe. During the sustained eruption that occurred in October-November 2002 huge amounts of volcanic ash fell on a densely populated area south-east of Mount Etna in Catania province. The volcanic ash fall caused extensive damage to infrastructure utilities and distress in the exposed population. This retrospective study evaluates whether or not there was an association between ash fall and acute health effects in exposed local communities. METHODS: We collected the number and type of visits to the emergency department (ED) for diseases that could be related to volcanic ash exposure in public hospitals of the Province of Catania between October 20 and November 7, 2002. We compared the magnitude of differences in ED visits between the ash exposure period in 2002 and the same period of the previous year 2001. RESULTS: We observed a significant increase of ED visits for acute respiratory and cardiovascular diseases, and ocular disturbances during the ash exposure time period. CONCLUSIONS: There was a positive association between exposure to volcanic ash from the 2002 eruption of Mount Etna and acute health effects in the Catania residents. This study documents the need for public health preparedness and response initiatives to protect nearby populations from exposure to ash fall from future eruptions of Mount Etna.

Type I Arnold-Chiari malformation with bronchiectasis, respiratory failure, and sleep disordered breathing: a case report.

Arnold Chiari Malformation (ACM) is defined as a condition where part of the cerebellar tissue herniates into the cervical canal toward the medulla and spinal cord resulting in a number of clinical manifestations. Type I ACM consists of variable displacement of the medulla throughout the formamen magnum into the cervical canal, with prominent cerebellar herniation.Type I ACM is characterized by symptoms related to the compression of craniovertebral junction, including ataxia, dysphagia, nistagmus, headache, dizziness, and sleep disordered breathing. We report a case of a life-long non-smoker, 54 years old woman who presented these symptoms associated with bronchiectasis secondary to recurrent inhalation pneumonia, hypercapnic respiratory failure, and central sleep apnea (CSA).CSA was first unsuccessfully treated with nocturnal c-PAP. The subsequent treatment with low flow oxygen led to breathing pattern stabilization with resolution of CSA and related clinical symptoms during sleep. We suggest that in patients with type I ACM the presence of pulmonary manifestations aggravating other respiratory disturbances including sleep disordered breathing (SDB) should be actively investigated. The early diagnosis is desirable in order to avoid serious and/or poorly reversible damages.

Bronchial cast hiding a lung cancer.

A 70-year-old man was admitted for severe hypoxia, haemoptysis and cough. Chest-X-ray and CT-scan indicated a right-lower-lobe collapse. Bronchoscopy showed its occlusion by whitish dense mucus. Aspiration revealed a Bronchial Cast (BC) and a stenotic and inflamed orifice of the right-lower-lobe-bronchus which was biopsied.Histopathologic examination of BC showed fibrin with lymphocytes and neutrophils, and, surprisingly, also the presence of lung cancer. Although the association between BC and benign, myxoid-soft-tissue, tracheobronchial tumors has been described, the association with lung cancer has not previously been reported, and it remains unclear whether it is causal or casual.

Prognostic value of p53 and Ki67 expression in fiberoptic bronchial biopsies of patients with non small cell lung cancer.

BACKGROUND: Overexpression of the tumor suppressor gene p53 and the marker for cellular proliferation Ki67 in open lung biopsies are indicated as predictor factors of survival of patients with lung cancer. However, the prognostic value of p53 and Ki67 in fiberoptic bronchial biopsies (FBB) has not been fully investigated. We evaluated p53 and Ki67 immunostaining in FBB from 19 with Non Small-Cell Lung Cancer (NSCLC: 12 adenocarcinomas, 5 squamous cell carcinomas and 2 NSCLC-NOS). METHODS: FBB specimens were fixed in formalin, embedded in paraffin, and immunostained using anti-p53 and anti-Ki67 antibodies. Slides were reviewed by two independent observers and classified as positive (+ve) when the number of cells with stained nuclei exceeded 15% for p53 or when >25% positive cells were observed throughout each section for Ki67. RESULTS: Positive (+ve) immunostaining was found in 9 patients for p53 (47.37%) and 8 patients for Ki67 (42.10%). We examined overall survival curves of the patients with Mantel's logrank test, both p53 -ve and Ki67 -ve patients had significantly higher survival rates than p53 + ve (p < 0.005) and Ki67 + ve (p < 0,0001), respectively. CONCLUSION: This study suggests that negative immunostaining of fiberoptic bronchial biopsies for p53 and Ki67 could represent a better prognostic factor for patients with NSCLC.

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome.

BACKGROUND: The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. OBJECTIVES: To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. SETTING: Sleep laboratory of Azienda Ospedaliera Garibaldi. PATIENTS: Twenty-five patients with moderate-to-severe OSA. DESIGN AND MEASUREMENTS: Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. RESULTS: The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. CONCLUSION: The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.