Standardizing PaO2 for PaCO2 in P/F ratio predicts in-hospital mortality in acute respiratory failure due to Covid-19: A pilot prospective study.

INTRODUCTION: Up to fifteen percent of patients with novel pandemic coronavirus disease (Covid-19) have acute respiratory failure (ARF). Ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, is currently used as a marker of ARF severity in Covid-19. P/F does not reflect the respiratory efforts made by patients to maintain arterial blood oxygenation, such as tachypnea and hyperpnea, leading to hypocapnia. Standard PaO2, the value of PaO2 adjusted for arterial partial pressure of carbon dioxide (PaCO2) of the subject, better reflects the pathophysiology of hypoxemic ARF. We hypothesized that the ratio between standard PaO2 over FiO2 (STP/F) better predicts Covid-19 ARF severity compared to P/F. METHODS: Aim of this pilot prospectic observational study was to observe differences between STP/F and P/F in predicting outcome failure, defined as need of invasive mechanical ventilation and/or deaths in Covid-19 ARF. Accuracy was calculated using Receiver Operating Characteristics (ROC) analysis and areas under the ROC curve (AUROC) were compared. RESULTS: 349 consecutive subjects admitted to our respiratory wards due to Covid-19 ARF were enrolled. STP/F was accurate to predict mortality and superior to P/F with, respectively, AUROC 0.710 versus 0.688, p = 0.012.Both STP/F and PF were accurate to predict outcome failure (AUROC respectively of 0.747 and 0.742, p = 0.590). DISCUSSION: This is the first study assessing the role of STP/F in describing severity of ARF in Covid-19. According to results, STP/F is accurate and superior to P/F in predicting in-hospital mortality.

Use of Symptoms Scores, Spirometry, and Other Pulmonary Function Testing for Asthma Monitoring.

Asthma is a global problem affecting millions of people all over the world. Monitoring of asthma both in children and in adulthood is an indispensable tool for the optimal disease management and for the maintenance of clinical stability. To date, several resources are available to assess the asthma control, first is the monitoring of symptoms, both through periodic follow-up visits and through specific quality of life measures addressed to the patient in first person or to parents. Clinical monitoring is not always sufficient to predict the risk of future exacerbations, which is why further instrumental examinations are available including lung function tests, the assessment of bronchial hyper-reactivity and bronchial inflammation. All these tools may help in quantifying the future risk for each patient and therefore they potentially may change the natural history of asthmatic disease. The monitoring of asthma in children as in adults is certainly linked by many aspects, however the asthmatic child is a future asthmatic adult and it is precisely during childhood and adolescence that we should implement all the efforts and strategies to prevent the progression of the disease and the subsequent impairment of lung function. For these reasons, asthma monitoring plays a crucial role and must be particularly close and careful. In this paper, we evaluate several tools currently available for asthma monitoring, focusing on current recommendations emerging from various guidelines and especially on the differences between the monitoring in pediatric age and adulthood.

Benefits of non-invasive ventilation in acute hypercapnic respiratory failure.

Non-invasive ventilation (NIV) with bilevel positive airway pressure is a non-invasive technique, which refers to the provision of ventilatory support through the patient's upper airway using a mask or similar device. This technique is successful in correcting hypoventilation. It has become widely accepted as the standard treatment for patients with hypercapnic respiratory failure (HRF). Since the 1980s, NIV has been used in intensive care units and, after initial anecdotal reports and larger series, a number of randomized trials have been conducted. Data from these trials have shown that NIV is a valuable treatment for HRF. This review aims to explore the principal areas in which NIV can be useful, focusing particularly on patients with acute HRF (AHRF). We will update the evidence base with the goal of supporting clinical practice. We provide a practical description of the main indications for NIV in AHRF and identify the group of patients with hypercapnic failure who will benefit most from the application of NIV.

Extracorporeal Lung Support for Hypercapnic Ventilatory Failure.

Extracorporeal lung support can be achieved using extracorporeal membrane oxygenation (ECMO) and extracorporeal CO2 removal. The ECMO systems allow a total lung support, providing both blood oxygenation and CO2 removal. Unlike ECMO, extracorporeal CO2 removal refers to an extracorporeal circuit that provides a partial lung support and selectively extracts CO2 from blood. The concept of partial extracorporeal lung support by removing only CO2 without effect on oxygenation was first proposed in 1977 by Kolobow and Gattinoni, with the aim to reduce breathing frequency, ventilator tidal volumes, and inspiratory pressures, facilitating lung-protective ventilation. Patients with end-stage chronic lung disease can survive, while waiting for lung transplantation, only if treated with mechanical ventilation or extracorporeal lung support. ECMO has been considered a suitable approach as a bridge to lung transplantation for patients with advanced respiratory failure waiting for lung transplantation. Extracorporeal CO2 removal has been proposed for the treatment of COPD patients suffering from exacerbation to avoid invasive mechanical ventilation. The rationale is to combine the improvement of alveolar ventilation by using noninvasive ventilation with muscle unload provided by removing CO2 directly from the blood, using an extracorporeal device. Increasing attention has been given to the possibility of patients performing a variety of physical activities while receiving extracorporeal lung support. This is possible thanks to the continuous development of technology together with the customization of sedative protocols. Awake extracorporeal support is a specific approach in which the patient is awake and potentially cooperative while receiving ECMO. The present analysis aims to synthesize the main results obtained by using extracorporeal circuits in patients with respiratory failure, particularly in those patients with hypercapnia.

Should I stay or should I go? COPD and air travel.

Chronic obstructive pulmonary disease (COPD) is a challenging respiratory problem throughout the world. Although survival is prolonged with new therapies and better management, the magnitude of the burden resulting from moderate-to-severe disease is increasing. One of the major aims of the disease management is to try to break the vicious cycle of patients being homebound and to promote an active lifestyle. A fundamental component of active daily life is, of course, travelling. Today, the world is getting smaller with the option of travelling by air. Air travel is usually the most preferred choice as it is easy, time saving, and relatively inexpensive. Although it is a safe choice for many passengers, the environment inside the aeroplane may sometimes have adverse effects on health. Hypobaric hypoxaemia due to cabin altitude may cause health risks in COPD patients who have limited cardiopulmonary reserve. Addressing the potential risks of air travel, promoting proactive strategies including pre-flight assessment, and education of COPD patients about the "fitness to fly" concept are essential. Thus, in this narrative review, we evaluated the current evidence for potential risks of air travel in COPD and tried to give a perspective for how to plan safe air travel for COPD patients.

Management of Dyspnea in the Terminally Ill.

The genesis of dyspnea involves the activation of several mechanisms that are mediated and perceived depending on previous experiences, values, emotions, and beliefs. Breathlessness may become unbearable, especially in patients who are terminally ill, whether afflicted by respiratory-, cardiac-, or cancer-related disorders, because of a final stage of a chronic process, an acute event, or both. Compared with pain, palliation of dyspnea has received relatively little attention in clinical practice and the medical literature. This is particularly true when the breathlessness is associated with acute respiratory failure because most of the studies on pharmacologic and nonpharmacologic treatments of respiratory distress have excluded such patients. Assessments of the quality of dying for patients in an ICU consistently show that few patients are considered by family members to breathe comfortably at the end of their life. This review focuses on the management of dyspnea in patients with advanced terminal illness, summarizing clinical trial evidence on pharmacologic and nonpharmacologic interventions available for these patients.

Magnetic Stimulation Therapy in Patients with COPD: A Systematic Review.

Magnetotherapy (MT) is a therapeutic treatment based on the use of magnetic fields (MF) that can have an anti-inflammatory and analgesic effect. MT represents a possible treatment or an ancillary therapeutic intervention for a wide range of diseases and it is often used in the field of physiotherapeutic practices. A crucial point in the treatment of chronic obstructive pulmonary disease (COPD) patients, to counteract muscular depletion and respiratory symptoms, is represented by physiotherapy. Nevertheless, the knowledge about the application of MF as a therapeutic option in COPD patients is very limited. The purpose of the present study was to define what is currently known about the use of MF in patients with COPD. A systematic review of the literature was conducted during the month of October 2017, searching three main databases. Only those citations providing detailed informations about the use of MF to treat COPD symptoms either during an acute or a chronic phase of the disease, were selected. Following the selection process three articles were included in the final analysis. The present review focused on a total of thirty-six patients with COPD, and on the effects of the application of MF. In the majority of cases, the treatment sessions with MF were carried-out in an outpatient setting, and they differed with regard to the duration; frequency of application; dosage; intensity of the applied MF. Basing on the available informations, it seems that MF is a feasible, well tolerated, safe therapeutic option, for the treatment of motor-related COPD symptoms.

Human Multidrug Resistance 1 gene polymorphisms and Idiopathic Pulmonary Fibrosis.

BACKGROUND: For the first time we tested an association between the human multidrug resistance gene 1 (MDR1) polymorphisms (SNPs) and idiopathic pulmonary fibrosis (IPF). Several MDR1 polymorphisms are associated with pathologies in which they modify the drug susceptibility and pharmacokinetics. MATERIALS AND METHODS: We genotyped three MDR1 polymorphisms of 48 IPF patients and 100 control subjects with Italian origins. RESULTS: No evidence of association was detected. CONCLUSION: There are 50 known MDR1 SNPs, and their role is explored in terms of the effectiveness of drug therapy. We consider our small-scale preliminary study as a starting point for further research.

Determinants of noninvasive ventilation outcomes during an episode of acute hypercapnic respiratory failure in chronic obstructive pulmonary disease: the effects of comorbidities and causes of respiratory failure.

OBJECTIVES: To investigate the effect of the cause of acute respiratory failure and the role of comorbidities both acute and chronic on the outcome of COPD patients admitted to Respiratory Intensive Care Unit (RICU) with acute respiratory failure and treated with NIV. DESIGN: Observational prospective study. PATIENTS AND METHODS: 176 COPD patients consecutively admitted to our RICU over a period of 3 years and treated with NIV were evaluated. In all patients demographic, clinical, and functional parameters were recorded including the cause of acute respiratory failure, SAPS II score, Charlson comorbidity index, and further comorbidities not listed in the Charlson index. NIV success was defined as clinical improvement leading to discharge to regular ward, while exitus or need for endotracheal intubation was considered failure. RESULTS: NIV outcome was successful in 134 patients while 42 underwent failure. Univariate analysis showed significantly higher SAP II score, Charlson index, prevalence of pneumonia, and lower serum albumin level in the failure group. Multivariate analysis confirmed a significant predictive value for pneumonia and albumin. CONCLUSIONS: The most important determinants of NIV outcome in COPD patients are the presence of pneumonia and the level of serum albumin as an indicator of the patient nutritional status.

Influence of the admission pattern on the outcome of patients admitted to a respiratory intensive care unit: does a step-down admission differ from a step-up one?

BACKGROUND: The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission. METHODS: We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality. RESULTS: Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality (P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a "ceiling treatment." The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death. CONCLUSIONS: The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.

Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes.

OBJECTIVES: This study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis. DESIGN AND METHODS: We genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis. RESULTS: Allelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)-c.1026-394G (rs7286680)-444C (rs10418) (OR=2.84; 95% C.I. 1.36-5.93, P value=0.004). CONCLUSIONS: This small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.

A role for epidermal growth factor receptor in idiopathic pulmonary fibrosis onset.

In idiopathic pulmonary fibrosis (IPF) patients the presence of missense polymorphisms (SNP) in members of the epidermal growth factor receptor (EGFR) family or their genetic association could influence the binding affinity of natural ligands, modifying the expression and the behavior of the correlated genes. EGFR family members are particularly involved in the epithelial injury and fibrotic process in IPF. Genetic variations in HER family of receptors may alter the possible therapeutic efficacy of EGFR inhibitors. This study aimed to analyze the relationships between IPF and specific EGF receptor family functional polymorphisms. We tested the presence of common EGFR, HER2 and HER3 non-synonymous SNPs in the peripheral blood of 20 Italian IPF patients and their association with the disease. Our data indicated that the HER2 variant allele frequency was significantly lower in patients than in controls, with an odds ratio of 0.31 (95% CI 0.080, 0.98). Our finding suggests that HER2 variant could be a protective factor against IPF onset.

Congenital cystic adenomatoid malformation of the lung associated with bronchial atresia involving a different lobe in an adult patient: a case report.

INTRODUCTION: Congenital cystic adenomatoid malformation of the lung is an uncommon cause of respiratory distress in neonates and babies. The disorder is usually diagnosed in the neonatal period and the first two years of life. This anomaly has been described in association with bronchopulmonary sequestration, extralobar intra-abdominal sequestration or bronchial atresia in live and stillborn babies. It is rarely encountered in adults, in whom the diagnosis is made incidentally from mass lesion features seen on chest radiographs. The oldest patients recorded with this malformation have been about 35 years old, and only 10% of primary diagnoses are made after the first year of life. Delayed diagnosis can be related to infection or serendipitous discovery. CASE PRESENTATION: We describe the radiological findings of a 34-year-old Caucasian woman with a clinical history of recurrent pneumonia, intermittent anterior pleuritic chest pain and haemoptysis. Congenital cystic adenomatoid malformation of the lung associated with bronchial atresia involving a different lobe was discovered. CONCLUSION: Although rare in adults, congenital cystic adenomatoid malformation should be suspected in adult patients who suffer from recurrent or persistent non-productive coughs. The discovery of an association of congenital cystic adenomatoid malformation with bronchial atresia in adulthood is rare but possible, even in different lobes.

Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening.

The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as > or =50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening.

Benign metastasizing leiomyoma of the lung: PET findings.

We report the case of pulmonary benign metastasizing leiomyoma in an asymptomatic 64-year-old woman who underwent hysterectomy for a uterine leiomyoma 26 years earlier. Routine chest radiograph revealed bilateral diffuse nodular opacities within the pulmonary lobes. Thoracic computed tomography (CT) scan showed peripheral lung nodules that do not display contrast enhancement. Positron emission tomography (PET)-CT with 18F-fluorodeoxyglucose (18F-FDG PET-CT) demonstrated no significant metabolic activity of the nodules. The lesions were diagnosed as benign metastasizing leiomyoma by histopathologic examination. To our best knowledge, this is the first case studied combining CT and FDG PET-CT technique.

The presence of emphysema further impairs physiologic function in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Emphysema, especially in the upper lobes, is frequently observed in association with idiopathic pulmonary fibrosis (IPF). However, the combination of emphysema plus IPF has received little attention. OBJECTIVE: To investigate the additional functional impairment from emphysema in IPF patients. METHODS: Twenty-one patients (mean age 66 y, 20 men) (Group I) who had both IPF (mean 35% of total lung volume) and emphysema (mean 14% of total lung volume) were compared to a group of 21 subjects who had IPF but no emphysema (Group II). The groups were matched for (among other criteria) the total extent of disease. Pulmonary function tests, Medical Research Council dyspnea score, 6-min walk test, and radiographic extents of both IPF and emphysema were obtained for each patient. The Composite Physiologic Index was calculated. In the total population (n = 42), the independent contributions of IPF and emphysema to several physiologic variables were investigated by using stepwise multiple regression analysis. RESULTS: Despite the limited extent of emphysema, Groups I and II had similar physiologic impairment. Only residual volume and total lung capacity were significantly higher in Group I. According to stepwise multiple regression analysis, the extent of IPF and either the presence or the extent of emphysema in the total population were independent and significant predictors of dyspnea score, 6-min walk test, P(aO2), forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), FEV1/FVC, the diffusing capacity of the lung for carbon monoxide, carbon monoxide diffusing capacity adjusted for alveolar volume (gas-transfer coefficient), and residual volume. The Composite Physiologic Index was closely related to the extent of IPF (r = 0.65, p < 0.0001) and to the dyspnea score (rho = 0.59, p < 0.0001). CONCLUSIONS: In former smokers with IPF, the presence and the extent of emphysema have a profound influence on physiologic function in terms of both further impairment and confounding effects.

Inflammatory activity is still present in the advanced stages of idiopathic pulmonary fibrosis.

OBJECTIVE: The role of active inflammation in idiopathic pulmonary fibrosis (IPF) is controversial. A gallium-67 citrate (Ga(67) scan) is a sensitive indicator of inflammatory activity. The aim of this study was to assess the Ga(67) uptake and other markers of inflammation at different stages of IPF and to investigate its prognostic role. METHODOLOGY: Twenty-two patients (aged 66 +/- 11 years, 18 males) with IPF were monitored for a period of 6-20 months (mean 13 months). At presentation (T0), high resolution CT (HRCT) scans showed reticular opacities and traction bronchiectasis with bi-basilar and peripheral distribution in all cases. At both T0 and follow-up (T1), we measured pulmonary function (PaO(2), FVC, DLco), overall radiographic extent of fibrosis (HRCT visual score), Ga(67) uptake, serum concentrations of lactate dehydrogenase (LDH) and C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). RESULTS: All parameters showed a significant deterioration during the T0-T1 interval, though the increase in Ga(67) uptake and serum markers was not significant. Patients with Ga(67) uptake indices graded as normal or mildly increased (group I), and graded as considerably or severely increased (group II) at presentation, were compared. There was no significant difference with respect to lung function or HRCT score between the two groups at T1. Ga(67) uptake, LDH, CRP and ESR at presentation did not correlate significantly with the interval change in pulmonary function and disease extent. CONCLUSIONS: Our findings indicate that inflammatory activity in the advanced stage of IPF is still relevant, although a Ga(67) scan is not predictive of the clinical course.

Bullous emphysema versus diffuse emphysema: a functional and radiologic comparison.

The contribution of bullous emphysema (BE) to the functional impairment of patients with concomitant diffuse emphysema (DE) and the confounding effects of BE on functional measurements were investigated. Twenty-nine patients (Group I), with BE and DE were compared with a group of patients without BE matched, among other criteria, for radiographic extent of DE (Group II). Group I showed significantly lower PaO2, FEV1 and DLCO values and higher MRC score than Group II. In Group I the radiographic extent of BE and the extent of DE did not predict the functional impairment. The FEV1/FVC ratio in the subgroup with BE extent > 25% of total lung volume was higher than in subgroups with BE extent > 20% and 15%, respectively. In the same subgroups the correlation between DE and DLCO increased with the extent of BE. We conclude that BE contributes to the functional impairment of patients with concomitant DE. The confounding functional effect of bullae depends on BE extent: relatively milder obstruction can be observed with severe BE, whereas moderate BE causes modest deterioration of diffusing capacity, explaining the lack of functional-radiologic correlations in Group I. Therefore the computed tomographic scan is very useful in the work-up of BE with DE associated.