Riccardo Pellegrino

Santa Croce e Carle General Hospital, Coni, Piedmont, Italy

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Publications (108)511.66 Total impact

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    ABSTRACT: Current guidelines recommend severity of chronic obstructive pulmonary disease be graded using forced expiratory volume in 1 s (FEV1). But this measurements is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis due to larger lung volumes and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution towards less severe classes in dominant emphysema more than chronic bronchitis. The Body mass, Obstruction, Dyspnea, and Exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended. Copyright © 2014, Journal of Applied Physiology.
    Journal of applied physiology (Bethesda, Md. : 1985). 11/2014;
  • Riccardo Pellegrino, Vito Brusasco
    Chest 09/2014; 146(3):541-542. · 7.13 Impact Factor
  • Riccardo Pellegrino, Vito Brusasco
    Chest 09/2014; 146(3):536-537. · 7.13 Impact Factor
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    ABSTRACT: Background and objectiveDuring forced expiration, alveolar pressure (PALV) increases and intrathoracic gas is compressed. Thus, 1-s forced expiratory volume measured by spirometry (FEV1-sp) is smaller than 1-s forced expiratory volume measured by plethysmography (FEV1-pl). Thoracic gas compression volume (TGCV) depends on the amount of gas within the lung when expiratory flow limitation occurs in the airways. We therefore tested the hypothesis that bronchoconstrictor and bronchodilator responses using FEV1-sp are biased by height and gender, which are major determinants of lung volume.Methods We studied 54 asthmatics during methacholine challenge and 55 subjects with airway obstruction (FEV1-sp increase >200 mL and >12% after salbutamol) measuring at the same time FEV1-sp or FEV1-pl.ResultsDuring methacholine challenge, TGCV increased more in males than females, correlated with PALV, total lung capacity (TLC) and height, and the provocative dose was lower using FEV1-sp than FEV1-pl. With salbutamol, FEV1-pl increased <200 mL and <12% in 28 subjects, predominantly tall males, with larger TLC, TGCV and PALV.Conclusions Bronchoconstrictor and bronchodilator responses are overestimated by standard spirometry in subjects with larger lungs because of TGCV.
    Respirology 08/2014; · 2.78 Impact Factor
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    ABSTRACT: Bronchial asthma is a chronic disease characterized by airway hyperresponsiveness, airway inflammation and remodelling. The hypothesis that the illness is inflammatory in nature has recently been challenged by studies showing that airway smooth muscle (ASM) plays a more important role than previously thought. For example, it is now known that in asthma patients, ASM proliferates more and faster than in healthy subjects, carries intrinsic defects and exhibits impaired relaxation, increased velocity of shortening, plastic adaptation to short length and perturbed equilibrium of actin-to-myosin during cycling. Similar conclusions can be drawn from studies on airway mechanics. For instance, in asthma, abnormal ASM contributes to limiting the response to deep lung stretching and accelerates the return of bronchial tone to baseline conditions, and contributes to increased airway stiffness. Upon stimulation, ASM causes airway narrowing that is heterogeneous across the lung and variable over time. This heterogeneity leads to patchy ventilation. Experimental studies have shown that patchy ventilation may precipitate an asthma attack, and inability to maintain bronchial tone control over time can predict the occurrence of bronchospastic attacks over a matter of a few days. To improve our knowledge on the pathogenesis of asthma, we believe that it is necessary to explore the disease within the framework of the topographical, volume and time domains of the lung that play an important role in setting the severity and progression of the disease. Application of the forced oscillation technique and multiple breath nitrogen washout may, alone or in combination, help address questions unsolvable until now.
    Respirology 08/2014; · 2.78 Impact Factor
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    ABSTRACT: Current opinion is that a vagal stimulation is beneficial for the cardiovascular apparatus but also causes airflow obstruction. The aim of this study was to examine this paradox. By using the within-breath Forced Oscillation Technique, inspiratory resistance and reactance at 5 Hz (R5 and X5, respectively) and cardio-vascular activity can be simultaneously measured humans at baseline and during baroreceptors stimulation by neck suction, allowing the study of the correlation between the parasympathetic activation and airway caliber. Correlation between changes in lung function and neck suction at 0.1Hz was tested in 15 volunteers using the cross-spectrum between either R5 or X5 and the stimulating waveform. Baroreceptors stimulation induced cardiovascular changes compatible with parasympathetic activation. The magnitude of the cross-spectrum between the pressure swings applied to the neck and both R5 and X5 presented a peak at 0.1 Hz with a higher coherence for R5 than X5. On average, R5 slightly but significantly increased compared to baseline, while changes in X5 were negligible. The response to the stimulation was highly variable among subjects.
    2014 8th Conference of the European Study Group on Cardiovascular Oscillations (ESGCO); 05/2014
  • Journal of Applied Physiology 04/2014; 116(8):1116-8. · 3.48 Impact Factor
  • Riccardo Pellegrino, Vito Brusasco, Martin R Miller
    European Respiratory Journal 04/2014; 43(4):947-8. · 6.36 Impact Factor
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    ABSTRACT: Obesity is associated with important decrements in lung volumes. Despite this, ventilation remains normally or near normally distributed at least for moderate decrements in functional residual capacity (FRC). We tested the hypothesis that this is because maximum flow increases presumably as a result of an increased lung elastic recoil. Forced expiratory flows corrected for thoracic gas compression volume, lung volumes, and forced oscillation technique at 5-11-19Hz were measured in 133 healthy subjects with a BMI ranging from 18 to 50 kg•m(-2). Short-term temporal variability of ventilation heterogeneity was estimated from the inter-quartile range of the frequency distribution of the difference in inspiratory resistance between 5 and 19 Hz (R5-19_IQR). FRC % predicted negatively correlated with body mass index (r= -0.72, p<0.001) and with an increase in slope of either maximal (r= -0.34, p<0.01) or partial flow-volume curves (r= -0.30, p<0.01). Together with a slight decrease in residual volume, this suggests an increased lung elastic recoil. Regression analysis of R5-19_IQR against FRC % predicted and expiratory reserve volume (ERV) yielded significantly higher correlation coefficients by non-linear than linear fitting models (r(2) = 0.40 vs. 0.30 for FRC% predicted and r(2) = 0.28 vs. 0.19 for ERV). In conclusion, temporal variability of ventilation heterogeneities increases in obesity only when FRC falls approximately below 65% of predicted or ERV below 0.6 L. Above these thresholds distribution is quite well preserved presumably as a result of an increase in lung recoil.
    Journal of Applied Physiology 03/2014; · 3.48 Impact Factor
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    ABSTRACT: Alveolar-capillary membrane conductance (DM,CO) and pulmonary capillary volume (VC) calculated assuming either infinite (∞) or finite (7.7) value for NO/CO blood conductance ratio in control subjects (open bars) and patients (black bars) two weeks before haematopoietic stem-cell transplantation. Data are mean ± standard deviation; *p < 0.001 vs. control subjects.
    Respiratory Physiology & Neurobiology 01/2014; · 2.05 Impact Factor
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    ABSTRACT: We hypothesized that dyspnea and its descriptors, that is, chest tightness, inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma reflect different mechanisms of airflow obstruction and their perception varies with the severity of bronchoconstriction. Eighty-three asthmatics were studied before and after inhalation of methacholine doses decreasing the 1-sec forced expiratory volume by ~15% (mild bronchoconstriction) and ~25% (moderate bronchoconstriction). Symptoms were examined as a function of changes in lung mechanics. Dyspnea increased with the severity of obstruction, mostly because of inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate analysis showed that dyspnea was related to the increase in inspiratory resistance at 5 Hz (R5) (r2 = 0.10, P = 0.004), chest tightness to the decrease in maximal flow at 40% of control forced vital capacity, and the increase in R5 at full lung inflation (r2 = 0.15, P = 0.006), inspiratory effort to the temporal variability in R5-19 (r2 = 0.13, P = 0.003), and unrewarded inspiration to the recovery of R5 after deep breath (r2 = 0.07, P = 0.01). At moderate bronchoconstriction, multivariate analysis showed that dyspnea and inspiratory effort were related to the increase in temporal variability in inspiratory reactance at 5 Hz (X5) (r2 = 0.12, P = 0.04 and r2 = 0.18, P < 0.001, respectively), and unrewarded inspiration to the decrease in X5 at maximum lung inflation (r2 = 0.07, P = 0.04). We conclude that symptom perception is partly explained by indexes of airway narrowing and loss of bronchodilatation with deep breath at low levels of bronchoconstriction, but by markers of ventilation heterogeneity and lung volume recruitment when bronchoconstriction becomes more severe.
    Physiological Reports. 12/2013; 1(7).
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    ABSTRACT: Inspiratory resistance (RINSP) and reactance (XINSP) were measured for 7min at 5 Hz in 10 mild asymptomatic asthmatics and 9 healthy subjects to assess the effects of airway smooth muscle (ASM) activation by methacholine (MCh) and unloading by chest wall strapping (CWS) on the variability of lung function and the effects of deep inspiration (DI). Subjects were studied at control conditions, after MCh, with CWS, and after MCh with CWS. In all experimental conditions XINSP was significantly more negative in asthmatic than healthy subjects, suggesting greater inhomogeneity in the former. However, the variability of both RINSP and XINSP was increased by either ASM activation or CWS, without significant difference between groups. DI significantly reversed MCh-induced changes in RINSP in both asthmatic and healthy subjects but XINSP in the former only. This effect was impaired by CWS more in the asthmatic than healthy subjects. The velocity of RINSP and XINSP recovery after deep inspiration was faster in asthmatic than healthy subjects. In conclusion, these results support the opinion that the short-term variability of respiratory impedance is related to ASM tone or operating length, rather than the disease. Nevertheless, asthmatic ASM differs from the healthy one for an increased velocity of shortening and a reduced sensitivity to mechanical stress when strain is reduced.
    Journal of Applied Physiology 06/2013; · 3.48 Impact Factor
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    ABSTRACT: Inspiratory resistance (RINSP) and reactance (XINSP) were measured for 7min at 5 Hz in 10 mild asymptomatic asthmatics and 9 healthy subjects to assess the effects of airway smooth muscle (ASM) activation by methacholine (MCh) and unloading by chest wall strapping (CWS) on the variability of lung function and the effects of deep inspiration (DI). Subjects were studied at control conditions, after MCh, with CWS, and after MCh with CWS. In all experimental conditions XINSP was significantly more negative in asthmatic than healthy subjects, suggesting greater inhomogeneity in the former. However, the variability of both RINSP and XINSP was increased by either ASM activation or CWS, without significant difference between groups. DI significantly reversed MCh-induced changes in RINSP in both asthmatic and healthy subjects but XINSP in the former only. This effect was impaired by CWS more in the asthmatic than healthy subjects. The velocity of RINSP and XINSP recovery after deep inspiration was faster in asthmatic than healthy subjects. In conclusion, these results support the opinion that the short-term variability of respiratory impedance is related to ASM tone or operating length, rather than the disease. Nevertheless, asthmatic ASM differs from the healthy one for an increased velocity of shortening and a reduced sensitivity to mechanical stress when strain is reduced.
    Journal of Applied Physiology 06/2013; · 3.48 Impact Factor
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    ABSTRACT: In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema. 22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(-1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (-13±7%, p = 0.001) and increased VCap (+20±22%, p = 0.016) and VE/VCO2 slope (+12±8%, p<0.01). These changes further increased after saline: -18±13% for DM (p<0.01), +44±28% for VCap (p<0.001), and +20±10% for VE/VCO2 slope (p<0.001). These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.
    PLoS ONE 01/2013; 8(4):e61877. · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Even after publication of the 2011 update of GOLD report, some fundamental questions in the management of COPD are still opened and remain unanswered and the lack of recommendations may weaken the applicability of these guidelines in everyday clinical practice. OBJECTIVE: To assess the level of consensus amongst Italian respirologists on different topics related to the diagnosis, monitoring and the role of bronchodilator therapy in COPD, by using the Delphi Technique. METHODS: A Delphi study was undertaken between July and November 2011, when two questionnaires were consecutively sent to a panel of experts to be answered anonymously. After each round, the data were aggregated at group level of question topics and structured feedback was given to the panel. RESULTS: Q1 was sent to 208 pulmonologists randomly selected from different Italian regions. The 132 respondents (63% of those initially selected) were from northern (53%), central (19%) and southern (28%) Italy. Q2 was sent to all the Q1 respondents, and a response was received from 110 of these (83%). The main topics that reached the pre-defined cut off for consensus (67% or more) were: a) bronchodilator therapy with long-acting bronchodilators could be beneficial in patients with airflow limitation even in the absence of symptoms, b) in patients not fully controlled with one long-acting bronchodilator, maximizing bronchodilation (i.e. adding another bronchodilator with a different mechanism of action) is the preferable option; and c) the use of ICSs as add on therapy should be considered in severe patients with frequent exacerbations. CONCLUSIONS: Italian specialists agree on several aspects of the diagnosis and treatment of COPD and expert opinion could support everyday decision process in the management of COPD.
    Pulmonary Pharmacology &amp Therapeutics 11/2012; · 2.54 Impact Factor
  • Riccardo Pellegrino, Andrea Antonelli
    European Respiratory Journal 10/2012; 40(4):801-3. · 6.36 Impact Factor
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    ABSTRACT: The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (G(rs)) at 5, 11 and 19Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (G(rs5)) were related to changes in lung volume (ΔG(rs5)/ΔV(L)) to estimate airway distensibility. G(rs) at FRC showed a slight but significant increase at all forcing frequencies by approximately 12-16%. TLC decreased after HSCT whereas the ΔG(rs5)/ΔV(L) ratio became higher after than before HSCT and was positively correlated (R(2)=0.87) with lung tissue density determined by quantitative CT scanning. We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT.
    Respiratory Physiology & Neurobiology 08/2012; 184(1):80-5. · 2.05 Impact Factor
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    ABSTRACT: Exercise in healthy subjects is usually associated with progressive bronchodilatation. Though the decrease in vagal tone is deemed to be the main underlying mechanism, activation of bronchial β(2)-receptors may constitute an additional cause. To examine the contribution of β(2)-adrenergic receptors to bronchodilatation during exercise in healthy humans, we studied 15 healthy male volunteers during maximum exercise test at control conditions and after a non-selective β-adrenergic blocker (carvedilol 12.5mg twice a day until heart rate decreased at least by 10beats/min) and inhaled β(2)-agonist (albuterol 400μg). Airway caliber was estimated from the partial flow at 40% of control forced vital capacity (V˙(part40)) and its changes during exercise from the slope of linear regression analysis of V˙(part40) values against the corresponding minute ventilation during maximal exercise until exhaustion. At control, V˙(part40) increased progressively and significantly with exercise. After albuterol, resting V˙(part40) was significantly larger than at control increased but did not further increase during exercise. After carvedilol, V˙(part40) was similar to control but its increase with exercise was significantly attenuated. These findings suggest that β(2)-adrenergic system plays a major role in exercise-induced bronchodilation in healthy subjects.
    Respiratory Physiology & Neurobiology 07/2012; 184(1):55-9. · 2.05 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 06/2012; 185(12):1330-1. · 11.04 Impact Factor
  • Riccardo Pellegrino, Vito Brusasco
    American Journal of Respiratory and Critical Care Medicine 04/2012; 185(8):896. · 11.04 Impact Factor

Publication Stats

6k Citations
511.66 Total Impact Points

Institutions

  • 2014
    • Santa Croce e Carle General Hospital
      Coni, Piedmont, Italy
  • 1996–2014
    • Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo
      Coni, Piedmont, Italy
  • 2013
    • University of Milan
      Milano, Lombardy, Italy
  • 2009–2012
    • Azienda Ospedaliera Universitaria San Martino di Genova
      Genova, Liguria, Italy
  • 2005–2010
    • Fondazione Salvatore Maugeri IRCCS
      • • Servizio di Fisiopatologia Respiratoria
      • • Unità Operativa di Riabilitazione Pneumologica
      Ticinum, Lombardy, Italy
    • University Hospitals Birmingham NHS Foundation Trust
      Birmingham, England, United Kingdom
    • Duke University Medical Center
      Durham, North Carolina, United States
    • Sapienza University of Rome
      • Department of Clinical Medicine
      Roma, Latium, Italy
  • 1994–2010
    • Università degli Studi di Genova
      • • Dipartimento di Medicina sperimentale (DIMES)
      • • Scuola di Scienze Mediche e Farmaceutiche
      Genova, Liguria, Italy
  • 2000–2008
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
  • 2002
    • Centro Cardiologico Monzino
      Milano, Lombardy, Italy
  • 1996–1999
    • Baylor College of Medicine
      • Department of Medicine
      Houston, TX, United States