Use of the combination of spirometry, arterial blood gas analysis and overnight oximetry to predict the outcomes of patients affected by motor neuron disease: The Milan-Torin respiratory score (Mi-To-RS).

BACKGROUND AND PURPOSE: The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better stratify their prognosis. MATERIALS AND METHODS: We screened the clinical charts of 471 non-ventilated MND patients referred to the Neuro-rehabilitation Unit of the San Raffaele Scientific Institute of Milan (January 2001-December 2019), collecting spirometric, ABG and OvOx parameters. To evaluate the prognostic role of each measurement, univariate Cox regression for death/tracheostomy was performed, and the variables associated with survival were selected to design a scoring system. Univariate and multivariate Cox regression analyses were then carried out to evaluate the prognostic role of the score. Finally, results were replicated in an independent cohort from the Turin ALS Center. RESULTS: The study population included 450 patients. Six measurements were found to be significantly associated with survival and were selected to design a scoring system (maximum score = 8 points). Kaplan-Meier analysis showed significant stratification of survival and time to non-invasive mechanical ventilation adaptation according to score values, and multivariate analysis confirmed the independent effect of the respiratory score on survival of each cohort. CONCLUSION: Forced vital capacity, ABG and OvOx parameters provide complementary information for the respiratory management and prognosis of MND patients and the combination of these parameters into a single score might help neurologists predict prognosis and guide decisions on the timing of the implementation of different diagnostic or therapeutic approaches.

Vertebral fractures at hospitalization predict impaired respiratory function during follow-up of COVID-19 survivors.

PURPOSE: Morphometric vertebral fractures (VFs) have been recently reported as an important component of the endocrine phenotype of COVID-19 and emerging data show negative respiratory sequelae at long-term follow-up in COVID-19 survivors. The aim of this study was to evaluate the impact of VFs on respiratory function in COVID-19 survivors. METHODS: We included patients referred to our Hospital Emergency Department and re-evaluated during follow-up. VFs were detected on lateral chest X-rays on admission using a qualitative and semiquantitative assessment and pulmonary function tests were obtained by Jaeger-MasterScreen-Analyzer Unit 6 months after discharge. RESULTS: Fifty patients were included. Median age was 66 years and 66% were males. No respiratory function data were available at COVID-19 diagnosis. VFs were detected in 16 (32%) patients. No differences between fractured and non-fractured patients regarding age and sex were observed. Although no difference was observed between VF and non-VF patient groups in the severity of pneumonia as assessed by Radiological-Assessment-of-Lung-Edema score at admission, (5 vs. 6, p = 0.69), patients with VFs were characterized as compared to those without VFs by lower Forced Vital Capacity (FVC, 2.9 vs. 3.6 L, p = 0.006; 85% vs. 110% of predicted, respectively, p = 0.001), Forced Expiratory Volume 1st s (FEV1, 2.2 vs. 2.8 L, p = 0.005; 92% vs. 110% of predicted, respectively, p = 0.001) and Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO 5.83 vs. 6.98 mmol/min/kPa, p = 0.036, 59% vs. 86.3% of predicted, respectively, p = 0.043) at 6-month follow up. CONCLUSIONS: VFs, expression of the endocrine phenotype of the disease, appear to influence medium-term impaired respiratory function of COVID-19 survivors which may significantly influence their recovery. Therefore, our findings suggest that a VFs assessment at baseline may help in identifying patients needing a more intensive respiratory follow-up and patients showing persistent respiratory impairment without evidence of pulmonary disease may benefit from VFs assessment to preventing the vicious circle of further fractures and respiratory deterioration.

Residual lung damage following ARDS in COVID-19 ICU survivors.

BACKGROUND: Coronavirus disease 2019 acute respiratory distress syndrome (COVID-19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID-19 ARDS sequelae. We assessed the mid-term lung status of COVID-19 survivors and investigated factors associated with pulmonary sequelae. METHODS: All adult COVID-19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. RESULTS: Forty-nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89-105) days, whilst PFT after 142 (133-160) days. The median age was 58 (52-65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6-16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71-7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO ) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9-93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. CONCLUSIONS: Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID-19.

Severe air pollution links to higher mortality in COVID-19 patients: The "double-hit" hypothesis.

OBJECTIVES: In areas of SARS-CoV-2 outbreak worldwide mean air pollutants concentrations vastly exceed the maximum limits. Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-CoV-2. The aim of this study was to analyse the relationship between air pollutants concentration (PM 2.5 and NO2) and COVID-19 outbreak, in terms of transmission, number of patients, severity of presentation and number of deaths. METHODS: COVID-19 cases, ICU admissions and mortality rate were correlated with severity of air pollution in the Italian regions. RESULTS: The highest number of COVID-19 cases were recorded in the most polluted regions with patients presenting with more severe forms of the disease requiring ICU admission. In these regions, mortality was two-fold higher than the other regions. CONCLUSIONS: From the data available we propose a "double-hit hypothesis": chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression. This may increase viral load in patients exposed to pollutants in turn depleting ACE-2 receptors and impairing host defences. High atmospheric NO2 may provide a second hit causing a severe form of SARS-CoV-2 in ACE-2 depleted lungs resulting in a worse outcome.

Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps?

BACKGROUND: The aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP. METHODS: 30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS. RESULTS: 18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1-26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 ± 11.1 versus 105 ± 5.9-p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05). CONCLUSION: In our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated.

Solitary fibrous tumour of the pleura presenting as a spontaneous massive haemothorax.

Solitary fibrous tumours of the pleura are rare neoplasms. These tumours are generally asymptomatic and incidentally diagnosed. Symptoms, if present, are nonspecific such as cough, dyspnea, and chest pain. This report describes the case of a 38-year-old woman admitted to our department after the onset of a right massive spontaneous haemothorax requiring emergency surgical treatment. Intraoperatively a bleeding pleural mass was found to be the cause of the haemothorax. The tumour was successfully resected and the patient made an uneventful recovery. Histological examination revealed the mass to be a solitary fibrous tumour of the pleura.

Peripheral baroreflex and chemoreflex function after eversion carotid endarterectomy.

OBJECTIVE: This study assessed the long-term effect of the eversion technique for carotid endarterectomy (e-CEA) on arterial baroreflex and peripheral chemoreflex function. METHODS: The study included 13 patients who underwent, between 2001 and 2006, bilateral e-CEA and 16 who underwent bilateral standard CEA (s-CEA) to eliminate the complicating effects of intact contralateral carotid sinus function. Exclusion criteria were age >70 years, diabetes mellitus, chronic pulmonary disease, ischemic cardiac disease or medical therapy with ß-blockers, cardiac arrhythmia, neurologic deficits, carotid restenosis, and previous neck or chest surgery or irradiation. Young and aged-matched healthy individuals were recruited as controls. All patients underwent standard cardiovascular reflex tests, including lying-to-standing, orthostatic hypotension, deep breathing, and Valsalva maneuver. Autonomic cardiovascular modulation was indirectly evaluated by spectral analysis of heart rate variability and systolic arterial pressure variability. The chemoreflex sensitivity to hypoxia was obtained during classic rebreathing tests from the slopes of the linear regression of minute ventilation (VE) vs arterial oxygen saturation measured by pulse oximetry (SpO2%) and partial pressure of end-tidal oxygen (PetO2). RESULTS: Patients (16 men; age, 62.4 ± 8.0 years) were enrolled after a mean interval of 24 ± 17 months from the last CEA. All were asymptomatic, and results of standard tests were negative. Residual baroreflex performance was documented in both patient groups, although reduced, compared with young controls. Notably, baroreflex sensitivity (msec/mm Hg) was better maintained after e-CEA than after s-CEA at rest (young controls, 19.93 ± 9.50; age-matched controls, 7.75 ± 5.68; e-CEA, 13.85 ± 14.54; and s-CEA, 3.83 ± 1.15; analysis of variance [ANOVA], P = .001); and at standing (young controls, 7.83 ± 2.55; age-matched controls, 3.71 ± 1.59; e-CEA, 7.04 ± 5.62; and s-CEA 3.57 ± 3.80; ANOVA, P = .001). Similarly, chemoreflex sensitivity to hypoxia was maintained in both patient groups, which did not differ from each other, and was reduced compared with controls (controls vs patient groups ΔVE/ΔSpO2: -1.37 ± 0.33 vs -0.33 ± 0.08 and SpO2% -0.29 ± 0.13 L/min; P = .002; ΔVE/ΔPetO2: -0.20 ± 0.1 vs -0.01 ± 0.0 and -0.07 ± 0.02 L/min/mm Hg; P = .04, ANOVA with least significant difference correction for multiple comparisons). CONCLUSIONS: Our data show that e-CEA, even when performed on both sides, preserves baroreflexes and chemoreflexes and, therefore, does not confer permanent carotid sinus denervation. Also, e-CEA does not increase long-term arterial pressure variability, and this suggests that perioperative hemodynamic derangements can be attributed to the temporary effects of surgical trauma.

Communication in a medical setting: can standards be improved?

Do standards exist to improve communication in a medical setting? What are the minimal requirements to make our communication with patients and their family clear and simple? International literature, as well as psychology, philosophy, and even our brain structure offer ways to improve communication. We reflected about what is preventing effective communication in the medical setting and how/from where should we set about improving it.

A geometrical approach to the PKPD modelling of inhaled bronchodilators.

The present work introduces a new method to model the pharmacokinetics (PK) and pharmacodynamics (PD) of an inhaled dose of bronchodilator, alternative to classic compartmental representations or computational fluid dynamics. A five compartment PK model comprising alimentary tract absorption (gut), bronchial tree mucosa, bronchial muscles, plasma, and elimination/excretion pathways has been developed. Many anatomical and physiological features of the bronchial tree depend on bronchial generation or on mean distance from the larynx. Among these are diameters, resistances, and receptor density, which determine together the local response to the inhaled drug; integrating these local responses over the whole bronchial tree allows an approximation of total bronchodilator response and airflow resistance. While the PK part of the model reflects classical compartmental assumptions, the PD part adds a simplified geometrical and functional description of the bronchial tree to a typical empirical model of local effect on bronchial muscle, leading to the direct computation of the approximate forced expiratory volume in 1 s (FEV(1)). In the present work the construction of the model is detailed, with reference to literature data. Simulation of a hypothetical asthmatic subject is employed to illustrate the behaviour of the model in representing the evolution over time of the distribution and pharmacological effect of an inhaled dose of a bronchodilator. The relevance of particle size and drug formulation diffusivity on therapeutic efficacy is discussed.

Mechanisms of gas exchange response to lung volume reduction surgery in severe emphysema.

Lung volume reduction surgery (LVRS) improves lung function, respiratory symptoms, and exercise tolerance in selected patients with chronic obstructive pulmonary disease, who have heterogeneous emphysema. However, the reported effects of LVRS on gas exchange are variable, even when lung function is improved. To clarify how LVRS affects gas exchange in chronic obstructive pulmonary disease, 23 patients were studied before LVRS, 14 of whom were again studied afterwards. We performed measurements of lung mechanics, pulmonary hemodynamics, and ventilation-perfusion (Va/Q) inequality using the multiple inert-gas elimination technique. LVRS improved arterial Po2 (Pa(O2)) by a mean of 6 Torr (P = 0.04), with no significant effect on arterial Pco2 (Pa(CO2)), but with great variability in both. Lung mechanical properties improved considerably more than did gas exchange. Post-LVRS Pa(O2) depended mostly on its pre-LVRS value, whereas improvement in Pa(O(2)) was explained mostly by improved Va/Q inequality, with lesser contributions from both increased ventilation and higher mixed venous Po(2). However, no index of lung mechanical properties correlated with Pa(O2). Conversely, post-LVRS Pa(CO2) bore no relationship to its pre-LVRS value, whereas changes in Pa(CO2) were tightly related (r² = 0.96) to variables, reflecting decrease in static lung hyperinflation (intrinsic positive end-expiratory pressure and residual volume/total lung capacity) and increase in airflow potential (tidal volume and maximal inspiratory pressure), but not to Va/Q distribution changes. Individual gas exchange responses to LVRS vary greatly, but can be explained by changes in combinations of determining variables that are different for oxygen and carbon dioxide.

Alveolar-derived exhaled nitric oxide is reduced in obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular diseases, in particular systemic arterial hypertension. We postulated that intermittent nocturnal hypoxia in OSAS may be associated to decreased fractional exhaled nitric oxide (FENO) levels from distal airspaces. METHODS: Multiple flow rate measurements have been used to fractionate nitric oxide (NO) from alveolar and bronchial sources in 34 patients with OSAS, in 29 healthy control subjects, and in 8 hypertensive non-OSAS patients. The effect of 2 days of treatment with nasal continuous positive airway pressure (nCPAP) on FENO was examined in 18 patients with severe OSAS. RESULTS: We found that the mean [+/- SE] concentrations of exhaled NO at a rate of 50 mL/s was 21.8 +/- 1.9 parts per billion (ppb) in patients with OSAS, 25.1 +/- 3.3 ppb in healthy control subjects, and 15.4 +/- 1.7 ppb in hypertensive control patients. The mean fractional alveolar NO concentration (CANO) in OSAS patients was significantly lower than that in control subjects (2.96 +/- 0.48 vs 5.35 +/- 0.83 ppb, respectively; p < 0.05). In addition, CANO values were significantly lower in OSAS patients with systemic hypertension compared to those in normotensive OSAS patients and hypertensive patients without OSAS. The mean values of CANO significantly improved after nCPAP therapy (2.67 +/- 0.41 to 4.69 +/- 0.74 nL/L, respectively; p = 0.01). CONCLUSIONS: These findings suggest that alveolar FENO, and not bronchial FENO, is impaired in patients with OSAS and that this impairment is associated with an increased risk of hypertension. NO production within the alveolar space is modified by treatment with nCPAP.

Localized organizing pneumonia: report of 21 cases.

BACKGROUND: Thoracic surgeons have limited experience with treating localized organizing pneumonia owing to its rare occurrence in routine clinical practice. METHODS: We retrospectively investigated the clinicopathologic features of 21 patients with localized organizing pneumonia observed between 2001 and 2004. RESULTS: There were 15 men and 6 women. Mean age was 63 years. Eight patients (38%) were symptomatic. Computed tomographic scan showed a single lesion in 17 patients (12 nodules and 5 masses) and bilateral lesions in 4. Wedge resection was performed in 16 patients and lobectomy in 5. There was no operative mortality. Follow-up was complete in all patients (range, 2 to 46 months; median, 20 months). Surgery was curative in 15 of 17 patients with a single lesion, and no recurrence was observed (p < 0.005). The remaining 2 patients with a single lesion (2 masses) had a local relapse with the appearance of nodular lesions in the residual parenchyma. Both these patients received steroids with resolution of the lesions. All 4 patients with bilateral lesions who underwent surgery for diagnostic purposes received steroids with improvement of the radiologic aspect in 3 and stabilization of the lesions in 1. CONCLUSIONS: Clinical and radiologic findings of localized organizing pneumonia are nonspecific, and this unusual entity is difficult to differentiate from a primary or metastatic tumor. Surgical resection allows both diagnosis and cure. However, considering the benignity of the lesion and the efficacy of steroids, major pulmonary resections should be avoided.

Autonomic cardiovascular regulation in subjects with acute mountain sickness.

The aims of this study were 1) to evaluate whether subjects suffering from acute mountain sickness (AMS) during exposure to high altitude have signs of autonomic dysfunction and 2) to verify whether autonomic variables at low altitude may identify subjects who are prone to develop AMS. Forty-one mountaineers were studied at 4,559-m altitude. AMS was diagnosed using the Lake Louise score, and autonomic cardiovascular function was explored using spectral analysis of R-R interval and blood pressure (BP) variability on 10-min resting recordings. Seventeen subjects (41%) had AMS. Subjects with AMS were older than those without AMS (P < 0.01). At high altitude, the low-frequency (LF) component of systolic BP variability (LF(SBP)) was higher (P = 0.02) and the LF component of R-R variability in normalized units (LF(RR)NU) was lower (P = 0.001) in subjects with AMS. After 3 mo, 21 subjects (43% with AMS) repeated the evaluation at low altitude at rest and in response to a hypoxic gas mixture. LF(RR)NU was similar in the two groups at baseline and during hypoxia at low altitude but increased only in subjects without AMS at high altitude (P < 0.001) and did not change between low and high altitude in subjects with AMS. Conversely, LF(SBP) increased significantly during short-term hypoxia only in subjects with AMS, who also had higher resting BP (P < 0.05) than those without AMS. Autonomic cardiovascular dysfunction accompanies AMS. Marked LF(SBP) response to short-term hypoxia identifies AMS-prone subjects, supporting the potential role of an exaggerated individual chemoreflex vasoconstrictive response to hypoxia in the genesis of AMS.

Diagnosis and treatment of traumatic pulmonary pseudocysts.

BACKGROUND: Traumatic pulmonary pseudocysts (TPPs) are rare sequelae of blunt chest trauma. We present a retrospective review of TPPs observed in our hospital and discuss the diagnosis, treatment, and complications of these unusual lesions. METHODS: Between 1991 and 1999, 11 TPPs were diagnosed in 10 patients. None of the lesions was detectable on the chest radiograph obtained on the day of injury. In contrast, computed tomographic scan of the chest always demonstrated the TPPs. RESULTS: In nine cases, spontaneous healing of the lesions was observed. One patient with a large lesion of the left lower lobe developed significant endobronchial bleeding and underwent successful emergency lobectomy. CONCLUSION: TPPs are often missed by chest radiography, particularly when it is obtained in the supine position, whereas computed tomographic scan allows the identification of these lesions in all cases. TPPs are self-limiting, benign lesions that usually require no specific therapy. Surgical treatment is indicated in rare instances and only when complications occur.

Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study.

BACKGROUND: High altitude pulmonary oedema (HAPE) that is severe enough to require urgent medical care is infrequent. We hypothesised that subclinical HAPE is far more frequent than suspected during even modest climbs of average effort. METHODS: We assessed 262 consecutive climbers of Monte Rosa (4559 m), before ascent and about 24 h later on the summit 1 h after arriving, by clinical examination, electrocardiography, oximetry, spirometry, carbon monoxide transfer, and closing volume. A chest radiograph was taken at altitude. FINDINGS: Only one climber was evacuated for HAPE, but 40 (15%) of 262 climbers had chest rales or interstitial oedema on radiograph after ascent. Of 37 of these climbers, 34 (92%) showed increased closing volume. Of the 197 climbers without oedema, 146 (74%) had an increase in closing volume at altitude. With no change in vital capacity, forced expiratory volume in 1 s and forced expiratory flow at 25-75% of forced vital capacity increased slightly at altitude, without evidence of oedema. If we assume that an increased closing volume at altitude indicates increased pulmonary extravascular fluid, our data suggest that three of every four healthy, recreational climbers have mild subclinical HAPE shortly after a modest climb. INTERPRETATION: The risk of HAPE might not be confined to a small group of genetically susceptible people, but likely exists for most climbers if the rate of ascent and degree of physical effort are great enough, especially if lung size is normal or low.