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1.  Challenges on non-invasive ventilation to treat acute respiratory failure in the elderly 
BMC Pulmonary Medicine  2016;16:150.
Acute respiratory failure is a frequent complication in elderly patients especially if suffering from chronic cardio-pulmonary diseases. Non-invasive mechanical ventilation constitutes a successful therapeutic tool in the elderly as, like in younger patients, it is able to prevent endotracheal intubation in a wide range of acute conditions; moreover, this ventilator technique is largely applied in the elderly in whom invasive mechanical ventilation is considered not appropriated. Furthermore, the integration of new technological devices, ethical issues and environment of treatment are still largely debated in the treatment of acute respiratory failure in the elderly.
This review aims at reporting and critically analyzing the peculiarities in the management of acute respiratory failure in elderly people, the role of noninvasive mechanical ventilation, the potential advantages of applying alternative or integrated therapeutic tools (i.e. high-flow nasal cannula oxygen therapy, non-invasive and invasive cough assist devices and low-flow carbon-dioxide extracorporeal systems), drawbacks in physician’s communication and “end of life” decisions. As several areas of this topic are not supported by evidence-based data, this report takes in account also “real-life” data as well as author’s experience.
The choice of the setting and of the timing of non-invasive mechanical ventilation in elderly people with advanced cardiopulmonary disease should be carefully evaluated together with the chance of using integrated or alternative supportive devices. Last but not least, economic and ethical issues may often challenges the behavior of the physicians towards elderly people who are hospitalized for acute respiratory failure at the end stage of their cardiopulmonary and neoplastic diseases.
PMCID: PMC5111281  PMID: 27846872
Acute respiratory failure; Non-invasive mechanical ventilation; Endotracheal intubation; End-of-life; High-flow nasal cannula; CO2-removal; Bronchoscopy; Elderly patient
2.  Amyloidosis involving the respiratory system: 5-year's experience of a multi-disciplinary group's activity 
Annals of Thoracic Medicine  2015;10(3):212-216.
Amyloidosis may involve the respiratory system with different clinical-radiological-functional patterns which are not always easy to be recognized. A good level of knowledge of the disease, an active integration of the pulmonologist within a multidisciplinary setting and a high level of clinical suspicion are necessary for an early diagnosis of respiratory amyloidosis. The aim of this retrospective study was to evaluate the number and the patterns of amyloidosis involving the respiratory system. We searched the cases of amyloidosis among patients attending the multidisciplinary rare and diffuse lung disease outpatients' clinic of Pulmonology Unit of the Hospital of Arezzo from 2007 to 2012. Among the 298 patients evaluated during the study period, we identified three cases of amyloidosis with involvement of the respiratory system, associated or not with other extra-thoracic localizations, whose diagnosis was histo-pathologically confirmed after the pulmonologist, the radiologist, and the pathologist evaluation. Our experience of a multidisciplinary team confirms that intra-thoracic amyloidosis is an uncommon disorder, representing 1.0% of the cases of rare and diffuse lung diseases referred to our center. The diagnosis of the disease is not always easy and quick as the amyloidosis may involve different parts of the respiratory system (airways, pleura, parenchyma). It is therefore recommended to remind this orphan disease in the differential diagnosis of the wide clinical scenarios the pulmonologist may intercept in clinical practice.
PMCID: PMC4518353  PMID: 26229565
Amyloidosis; lung amyloidosis; pleural amyloidosis; pulmonary amyloidosis; respiratory system
3.  Non-invasive mechanical ventilation in patients with diffuse interstitial lung diseases 
BMC Pulmonary Medicine  2014;14:194.
To evaluate noninvasive ventilation (NIV) in diffuse interstitial lung diseases (DILD) patients with acute respiratory failure (ARF) according to baseline radiological patterns and the etiology of ARF.
In a multicenter, observational, retrospective study, consecutive DILD patients undergoing NIV because of an episode of ARF were evaluated in six Italian high dependency units. Three groups of patients were identified based on the etiology of ARF: those with pneumonia (Group A), those with acute exacerbation of fibrosis, (Group B) and those with other triggers (Group C). Clinical failure was defined as any among in-hospital mortality, endotracheal intubation and extra-corporeal membrane oxygenation use.
Among the 60 patients enrolled (63% males; median age: 71 years), pneumonia (42%) and acute exacerbation of fibrosis (39%) were the two most frequent causes of ARF. A significant increase of PaO2/FiO2 ratio during NIV treatment was detected in Group A (p = 0.010), but not in Group B. No significant difference in PaO2/FiO2 ratio, PaCO2 and pH values during NIV treatment was detected in patients with a radiological pattern of usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). 22 patients (37%) suffered for a clinical failure. No significant differences in the study outcome were detected in Group A vs. Group B, as well as among patients with a radiological pattern of UIP vs. NSIP.
NIV treatment should be individualized in DILD patients with ARF according to the etiology, but not the baseline radiological pattern, in order to improve oxygenation.
PMCID: PMC4269964  PMID: 25476922
Fibrosis; Diffuse parenchymal lung disease; Non-invasive ventilation; Interstitial lung disease; Pneumonia; Continuous positive airway pressure; Ventilation
4.  Small Airway Impairment and Bronchial Hyperresponsiveness in Asthma Onset 
Our study tried to find a relationship between baseline FEF25-75% and airway hyperresponsiveness (AHR) and whether a greater FEF25-75% impairment may be a marker of a more severe hyperresponsiveness in subjects with normal FEV1 and FEV1/FVC and suggestive asthma symptoms. Besides, we tried to asses a FEF25-75% cut-off value to identify hyper-reactive subjects.
4,172 subjects (2,042 M; mean age: 38.3±14.9; mean FEV1 % predicted: 100.5±12.7 and FEV1/FVC: 85.4±6.8) were examined after performing a methacholine (Mch) test. All subjects reported a symptom onset within 3 years before the test. Subjects with PD20<400 or >400 µg were arbitrarily considered affected by moderate/severe and borderline AHR, respectively.
PD20 values were 213 (IQR:86-557), 340 (IQR:157-872) and 433 (IQR:196-1032) µg in subjects with baseline FEF25-75≤50%, FEF25-75 between 50 and 70% and FEF25-75>70% respectively (P<0.0001). Only in moderate/severe hyper-reactive subjects (excluded borderlines), PD20 was lower in the FEF25-75≤50% subgroup than in the 1 with FEF25-75>70%. The hyperreactive subjects percentage, was higher in those with FEF25-75≤50% and lower in those with FEF25-75>70% (P<0.0001). FEF25-75<50% (compared to FEF25-75>70%) was a higher AHR risk factor, especially in subjects with moderate/severe AHR (OR: 2.18 [IQR:1.41-3.37]; P<0.0001). Thresholds yielding the highest combined sensitivity/specificity for FEF25-75% were 75.19 (area under curve [AUC]: 0.653) and 74.95 (AUC:0.688) in subjects with PD20<2,400 and <400 µg respectively. FEV1, FVC, and FEV1/FVC measured in subjects with different FEF25-75≤50%, FEF25-75>50 and ≤70% or FEF25-75>70% levels were similar both in normoreactive and hyperreactive subjects.
At asthma onset, reduced baseline FEF25-75 values with normal FEV1 and FEV1/FVC may predict AHR. Detectable predictive cut-off values do not exist because even normoreactive subjects can show lower FEF25-75 values. Furthermore, a greater FEF25-75 reduction may be associated to a more severe AHR, suggesting a possible FEF25-75 role in the management of asthma when FEV1 and FEV1/FVC are normal.
PMCID: PMC4021243  PMID: 24843800
Airway hyperresponsiveness; small airways; methacholine test; asthma; FEF25-75; diagnosis
5.  Obesity can influence children’s and adolescents’ airway hyperresponsiveness differently 
Literature is still arguing about a possible relationship between airway hyperresponsiveness (AHR) and body mass index (BMI). This study aimed at evaluating the influence of BMI on AHR and pulmonary function in children and adolescents that performed a methacholine test for suggestive asthma symptoms.
799 consecutive children/adolescents (535 M; mean age: 15 ± 3 yrs; median FEV1% predicted: 101.94% [93.46-111.95] and FEV1/FVC predicted: 91.07 [86.17-95.38]), were considered and divided into underweight, normal, overweight and obese. Different AHR levels were considered as moderate/severe (PD20 ≤ 400 μg) and borderline (PD20 > 400 μg).
536 children/adolescents resulted hyperreactive with a median PD20 of 366 μg [IQR:168–1010.5]; 317 patients were affected by moderate/severe AHR, whereas 219 showed borderline hyperresponsiveness. Obese subjects aged > 13 years showed a lower (p = 0.026) median PD20 (187μg [IQR:110–519]) compared to overweight (377 μg [IQR:204–774]) and normal-weight individuals’ values (370.5 μg [IQR:189–877]). On the contrary, median PD20 observed in obese children aged ≤ 13 years (761 μg [IQR:731–1212]) was higher (p = 0.052) compared to normal-weight children’s PD20 (193 μg [IQR:81–542]) and to obese adolescents’ values (aged > 13 years) (p = 0.019). Obesity was a significant AHR risk factor (OR:2.853[1.037-7.855]; p = 0.042) in moderate/severe AHR adolescents. Females showed a higher AHR risk (OR:1.696[1.046-2.751] p = 0.032) compared to males. A significant relationship was found between BMI and functional parameters (FEV1, FVC, FEV1/FVC) only in hyperreactive females.
Obesity seems to influence AHR negatively in female but not in male adolescents and children. In fact, AHR is higher in obese teenagers, in particular in those with moderate/severe hyperresponsiveness, and may be mediated by obesity-associated changes in baseline lung function.
PMCID: PMC3844670  PMID: 24028436
Airway hyperresponsiveness; Asthma; Body mass index; Children and adolescents; Methacholine test; Obesity
7.  Clinical review: Humidifiers during non-invasive ventilation - key topics and practical implications 
Critical Care  2012;16(1):203.
Inadequate gas conditioning during non-invasive ventilation (NIV) can impair the anatomy and function of nasal mucosa. The resulting symptoms may have a negative effect on patients' adherence to ventilatory treatment, especially for chronic use. Several parameters, mostly technical aspects of NIV, contribute to inefficient gas conditioning. Factors affecting airway humidity during NIV include inspiratory flow, inspiratory oxygen fraction, leaks, type of ventilator, interface used to deliver NIV, temperature and pressure of inhaled gas, and type of humidifier. The correct application of a humidification system may avoid the effects of NIV-induced drying of the airway. This brief review analyses the consequences of airway dryness in patients receiving NIV and the technical tools necessary to guarantee adequate gas conditioning during ventilatory treatment. Open questions remain about the timing of gas conditioning for acute or chronic settings, the choice and type of humidification device, the interaction between the humidifier and the underlying disease, and the effects of individual humidification systems on delivered humidity.
PMCID: PMC3396215  PMID: 22316078
8.  BMI can influence adult males’ and females’ airway hyperresponsiveness differently 
Epidemiological data indicate that obesity is a risk factor for asthma, but scientific literature is still debating the association between changes in body mass index (BMI) and airway hyperresponsiveness (AHR).
This study aimed at evaluating the influence of BMI on AHR, in outpatients with symptoms suggestive of asthma.
4,217 consecutive adult subjects (2,439 M; mean age: 38.2±14.9 yrs; median FEV1 % predicted: 100 [IQR:91.88-107.97] and FEV1/FVC % predicted: 85.77% [IQR:81.1-90.05]), performed a methacholine challenge test for suspected asthma. Subjects with PD20 < 200 or 200 < PD20 < 800 or PD20 > 800 were considered affected by severe, moderate or mild AHR, respectively.
A total of 2,520 subjects (60% of all cases) had a PD20 < 3,200 μg, with a median PD20 of 366 μg [IQR:168–1010.5]; 759, 997 and 764 patients were affected by mild, moderate and severe AHR, respectively. BMI was not associated with increasing AHR in males. On the contrary, obese females were at risk for AHR only when those with moderate AHR were considered (OR: 1.772 [1.250-2.512], p = 0.001). A significant reduction of FEV1/FVC for unit of BMI increase was found in moderate AHR, both in males (β = −0.255; p =0.023) and in females (β = −0.451; p =0.017).
Our findings indicate that obesity influences AHR only in females with a moderate AHR level. This influence may be mediated by obesity-associated changes in baseline lung function.
PMCID: PMC3529699  PMID: 23157852
Airway hyperresponsiveness; asthma; body mass index; males and females; methacholine test; obesity
9.  Seasons can influence the results of the methacholine challenge test 
Annals of Thoracic Medicine  2012;7(2):61-68.
This study tried to evaluate whether a methacholine test may be influenced by the seasons.
We considered 4826 consecutive subjects with normal spirometry (50.53% males; age: 35.1±16.2; forced expiratory volume in one second: 99.5±13.0%) who underwent a methacholine test for suspected asthma symptoms between 2000 and 2010. They were subdivided into four groups, like the seasons, according to the test dates.
A total of 1981 (41%) resulted normal (no PD20 was obtained with 2400 μg of methacholine); the others showed a mean LogPD20 of 2.52±0.5 μg. The number of subjects with bronchial hyper-responsiveness (BHR) found in autumn (789, 62.3%) was higher than in summer (583, 56.7%; P=0.03). A higher number of females and overweight/obese subjects showed a BHR in autumn compared with the other seasons. The spring mean LogPD20 value (2.48±0.48 μg) was lower if compared with the one measured in summer (2.59±0.49 μg; P=0.05). LogPD20 value was lower in females and non-smokers in spring compared with summer (P<0.05). Overweight/obese non-smokers showed a lower LogPD20 in spring and autumn compared with that in summer (P<0.05). Autumn was a risk factor (OR: 1.378; P=0.001) for BHR (using a PD20 <2 400 μg as BHR limit), while spring (OR: 1.330; P=0.021) and autumn (OR: 1.331; P=0.020) were risk factors for a more severe BHR (using a PD20 <400 μg as BHR limit).
There was a higher probability of finding BHR in outpatients with suspected asthma in autumn and spring compared with summer. Spring is the season where BHR may be more severe. Females and overweight/obese subjects were those mainly involved in this seasonal variability of BHR.
PMCID: PMC3339205  PMID: 22558009
Airway; asthma; bronchial hyper-responsiveness; methacholine challenge test; season
10.  Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial 
Critical Care  2011;15(6):R283.
The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven.
The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled.
Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization.
The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged.
Trial registration NCT01291303.
PMCID: PMC3388700  PMID: 22115190
chronic obstructive pulmonary disease; acute exacerbation; non invasive ventilation; ventilators
11.  Early fiberoptic bronchoscopy during non-invasive ventilation in patients with decompensated chronic obstructive pulmonary disease due to community-acquired-pneumonia 
Critical Care  2010;14(2):R80.
Inefficient clearance of copious respiratory secretion is a cause of non-invasive positive pressure ventilation (NPPV) failure, especially in chronic respiratory patients with community-acquired-pneumonia (CAP) and impaired consciousness. We postulated that in such a clinical scenario, when intubation and conventional mechanical ventilation (CMV) are strongly recommended, the suction of secretions with fiberoptic bronchoscopy (FBO) may increase the chance of NPPV success. The objective of this pilot study was, firstly, to verify the safety and effectiveness of early FBO during NPPV and, secondly, to compare the hospital outcomes of this strategy versus a CMV-based strategy in patients with decompensated chronic obstructive pulmonary disease (COPD) due to CAP who are not appropriate candidates for NPPV because of inefficient mucous clearance and hypercapnic encephalopathy (HE).
This is a 12-month prospective matched case-control study performed in one respiratory semi-intensive care unit (RSICU) with expertise in NPPV and in one intensive care unit (ICU). Fifteen acutely decompensated COPD patients with copious secretion retention and HE due to CAP undergoing NPPV in RSICU, and 15 controls (matched for arterial blood gases, acute physiology and chronic health evaluation score III, Kelly-Matthay scale, pneumonia extension and severity) receiving CMV in the ICU were studied.
Two hours of NPPV significantly improved arterial blood gases, Kelly and cough efficiency scores without FBO-related complications. NPPV avoided intubation in 12/15 patients (80%). Improvement in arterial blood gases was similar in the two groups, except for a greater PaO2/fraction of inspired oxygen ratio with CMV. The rates of overall and septic complications, and of tracheostomy were lower in the NPPV group (20%, 20%, and 0%) versus the CMV group (80%, 60%, and 40%; P < 0.05). Hospital mortality, duration of hospitalisation and duration of ventilation were similar in the two groups.
In patients with decompensated COPD due to CAP who are candidates for CMV because of HE and inability to clear copious secretions, NPPV with early therapeutic FBO performed by an experienced team is a feasible, safe and effective alternative strategy.
PMCID: PMC2887203  PMID: 20429929

Results 1-11 (11)