Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

Harrison, T. W.; Chanez, P.; Menzella, F.; Canonica, G. W.; Louis, R.; Cosio, B. G.; Lugogo, N. L.; Mohan, A.; Burden, A.; Mcdermott, L.; Garcia Gil, E.; Zangrilli, J. G.; Pohl, W.; Voves, R.; Deschampheleire, M.; Martinot, J. -B.; Peche, R.; Chapman, K.; Cheema, A.; Dorscheid, D.; Fitzgerald, J. M.; Gagnon, R.; Killorn, W. P.; Olivenstein, R.; Philteos, G.; Ramsey, C.; Rolf, J. D.; Walker, B.; Hilberg, O.; Skjold, T.; Titlestad, I.; Hakulinen, A.; Kilpelainen, M.; Ben Hayoun, M.; Bonniaud, P.; Bourdin, A.; De Blay, F.; Deslee, G.; Devouassoux, G.; Didier, A.; Douadi, Y.; Fry, S.; Garcia, G.; Girodet, P. -O.; Leroyer, C.; Magnan, A.; Mahay, G.; Nocent, C.; Pison, C.; Roux, P. -M.; Taille, C.; Tiotiu, J. -A.; Beck, E.; Jandl, M.; Kaehler, C.; Kassner, F.; Koesters, F.; Kronsbein, J.; Schaum, T.; Schulz, C.; Skowasch, D.; Taube, C.; Welte, T.; de Roux, A.; Bianca, Beghe; Blasi, F.; Carpagnano, G.; Caruso, C.; Corsico, A. G.; Constantino, E.; Crimi, N.; Maestrelli, P.; Milanese, M.; Papi, A.; Pelaia, G.; Pini, L.; Santus, P.; Savi, E.; Scichilone, N.; Senna, G.; Spadaro, G.; Vaghi, A.; Gans, S.; Holters, J.; Langeveld, B.; Pieters, W.; Staaks, G. H. A.; van Veen, I.; van den Berg, J. W. K.; Einvik, G.; Lehmann, S.; Ali Garcia, I.; Almonacid, C.; Bobolea, I.; Campo Mozo, P.; de Luiz, G.; Domingo Ribas, C.; Echave-Sustaeta Maria-Tome, J. M.; Garcia Rivero, J. L.; Garcia-Cosio Piqueras, B.; Gomez-Bastero Fernandez, A.; Gonzalez Perez, R.; Henriquez Santa, A.; Martinez Rivera, C.; Munoz Gall, X.; Ramos, J.; Gregorio Soto Campos, J.; Vidal Pan, C.; Stenfors, N.; Tunsater, A.; Vinge, I.; Chaudhuri, R.; Harrison, T.; Mansur, A.; Nasser, S.; Nordstrom, M.; Pfeffer, P.; Saralaya, D.; Short, P.; Adlakha, A.; Alpan, O.; Averill, F.; Badhwar, A.; Bardelas, J.; Baxter, B.; Bensch, G.; Berger, W.; Bernstein, J.; Bridges, T.; Brimeyer, R.; Calhoun, W.; Campbell, E.; Cherry, W. B.; Chupp, G.; Clore, L.; Cohn, J.; Cole, J.; Condemi, J.; Cury, J.; Davis, B.; Deleon, S.; Delacruz, L.; Diaz, J.; Erb, D.; Eziri, E.; Fakih, F.; Fiedler, D.; Fost, D.; Fritz, S.; Gonzalez, E.; Goodman, B.; Gottlieb, P.; Gottschlich, G.; Gower, R.; Hajal, R.; Harris, J.; Heidarian-Raissy, H.; Heyder, A.; Hill, D.; Holguin, F.; Hussain, I.; Illowite, J.; Jacobs, J.; Jarratt, M.; Kaiser, H.; Kao, N.; Kashyap, R.; Kaufman, D.; Kent, E.; Kim, K.; Klein, R.; Kraft, M.; Kono, R.; Kureishy, S.; Leflein, J.; Leong, M.; Li, H.; Lin, R.; Lugogo, N.; Marcus, M.; Maselli Caceres, D. J.; Mehta, V.; Mello, C.; Millard, M.; Milstone, A.; Moore, W.; Moss, M.; Mumneh, N.; O'Brien, T.; Ostransky, D.; Palumbo, M.; Parikh, P.; Parikh, S.; Patel, A.; Perez, G.; Pleskow, W.; Prenner, B.; Puppala, D.; Ramey, J.; Reibman, J.; Reyes, R.; Robinette, E.; Rodicio, I.; Ryan, S.; Sekhsaria, S.; Sigal, B.; Sikand, V.; Soong, W.; Spangenthal, S.; t. John R., S; Steven, G.; Subramaniam, V.; Sumino, K.; Sztejman, E.; Tan, R. A.; Tanus, T.; Thompson, C.; Thornblade, C.; Villareal, M.; Wenzel, S.; Zafra, H.; Ziedalski, T.

doi:10.1016/S2213-2600(20)30414-8

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p<0·0001) over the 24-week treatment period and provided clinically meaningful and statistically significant improvement from baseline to week 24 in SGRQ total score versus placebo (least squares mean change from baseline −8·11 (95% CI −11·41 to −4·82; p<0·0001), with similar differences at earlier timepoints. Benralizumab improved FEV1, PEF, ACQ-6, CGI-C, PGI-C, PSIA, and SNOT-22 at week 24 versus placebo, with differences observed early (within weeks 1 to 4). Adverse events were reported for 271 (63%) of 427 patients on benralizumab versus 143 (62%) of 229 patients on placebo. The most commonly reported adverse events for the 427 patients receiving benralizumab (frequency >5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial / Harrison, T. W.; Chanez, P.; Menzella, F.; Canonica, G. W.; Louis, R.; Cosio, B. G.; Lugogo, N. L.; Mohan, A.; Burden, A.; Mcdermott, L.; Garcia Gil, E.; Zangrilli, J. G.; Pohl, W.; Voves, R.; Deschampheleire, M.; Martinot, J. -B.; Peche, R.; Chapman, K.; Cheema, A.; Dorscheid, D.; Fitzgerald, J. M.; Gagnon, R.; Killorn, W. P.; Olivenstein, R.; Philteos, G.; Ramsey, C.; Rolf, J. D.; Walker, B.; Hilberg, O.; Skjold, T.; Titlestad, I.; Hakulinen, A.; Kilpelainen, M.; Ben Hayoun, M.; Bonniaud, P.; Bourdin, A.; De Blay, F.; Deslee, G.; Devouassoux, G.; Didier, A.; Douadi, Y.; Fry, S.; Garcia, G.; Girodet, P. -O.; Leroyer, C.; Magnan, A.; Mahay, G.; Nocent, C.; Pison, C.; Roux, P. -M.; Taille, C.; Tiotiu, J. -A.; Beck, E.; Jandl, M.; Kaehler, C.; Kassner, F.; Koesters, F.; Kronsbein, J.; Schaum, T.; Schulz, C.; Skowasch, D.; Taube, C.; Welte, T.; de Roux, A.; Beghe, Bianca; Blasi, F.; Carpagnano, G.; Caruso, C.; Corsico, A. G.; Constantino, E.; Crimi, N.; Maestrelli, P.; Milanese, M.; Papi, A.; Pelaia, G.; Pini, L.; Santus, P.; Savi, E.; Scichilone, N.; Senna, G.; Spadaro, G.; Vaghi, A.; Gans, S.; Holters, J.; Langeveld, B.; Pieters, W.; Staaks, G. H. A.; van Veen, I.; van den Berg, J. W. K.; Einvik, G.; Lehmann, S.; Ali Garcia, I.; Almonacid, C.; Bobolea, I.; Campo Mozo, P.; de Luiz, G.; Domingo Ribas, C.; Echave-Sustaeta Maria-Tome, J. M.; Garcia Rivero, J. L.; Garcia-Cosio Piqueras, B.; Gomez-Bastero Fernandez, A.; Gonzalez Perez, R.; Henriquez Santa, A.; Martinez Rivera, C.; Munoz Gall, X.; Ramos, J.; Gregorio Soto Campos, J.; Vidal Pan, C.; Stenfors, N.; Tunsater, A.; Vinge, I.; Chaudhuri, R.; Harrison, T.; Mansur, A.; Nasser, S.; Nordstrom, M.; Pfeffer, P.; Saralaya, D.; Short, P.; Adlakha, A.; Alpan, O.; Averill, F.; Badhwar, A.; Bardelas, J.; Baxter, B.; Bensch, G.; Berger, W.; Bernstein, J.; Bridges, T.; Brimeyer, R.; Calhoun, W.; Campbell, E.; Cherry, W. B.; Chupp, G.; Clore, L.; Cohn, J.; Cole, J.; Condemi, J.; Cury, J.; Davis, B.; Deleon, S.; Delacruz, L.; Diaz, J.; Erb, D.; Eziri, E.; Fakih, F.; Fiedler, D.; Fost, D.; Fritz, S.; Gonzalez, E.; Goodman, B.; Gottlieb, P.; Gottschlich, G.; Gower, R.; Hajal, R.; Harris, J.; Heidarian-Raissy, H.; Heyder, A.; Hill, D.; Holguin, F.; Hussain, I.; Illowite, J.; Jacobs, J.; Jarratt, M.; Kaiser, H.; Kao, N.; Kashyap, R.; Kaufman, D.; Kent, E.; Kim, K.; Klein, R.; Kraft, M.; Kono, R.; Kureishy, S.; Leflein, J.; Leong, M.; Li, H.; Lin, R.; Lugogo, N.; Marcus, M.; Maselli Caceres, D. J.; Mehta, V.; Mello, C.; Millard, M.; Milstone, A.; Moore, W.; Moss, M.; Mumneh, N.; O'Brien, T.; Ostransky, D.; Palumbo, M.; Parikh, P.; Parikh, S.; Patel, A.; Perez, G.; Pleskow, W.; Prenner, B.; Puppala, D.; Ramey, J.; Reibman, J.; Reyes, R.; Robinette, E.; Rodicio, I.; Ryan, S.; Sekhsaria, S.; Sigal, B.; Sikand, V.; Soong, W.; Spangenthal, S.; S, t. John R.; Steven, G.; Subramaniam, V.; Sumino, K.; Sztejman, E.; Tan, R. A.; Tanus, T.; Thompson, C.; Thornblade, C.; Villareal, M.; Wenzel, S.; Zafra, H.; Ziedalski, T.. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - 9:3(2021), pp. 260-274. [10.1016/S2213-2600(20)30414-8]

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

Harrison T. W.;Chanez P.;Menzella F.;Canonica G. W.;Louis R.;Cosio B. G.;Lugogo N. L.;Mohan A.;Burden A.;McDermott L.;Garcia Gil E.;Zangrilli J. G.;Pohl W.;Voves R.;Deschampheleire M.;Martinot J. -B.;Peche R.;Chapman K.;Cheema A.;Dorscheid D.;FitzGerald J. M.;Gagnon R.;Killorn W. P.;Olivenstein R.;Philteos G.;Ramsey C.;Rolf J. D.;Walker B.;Hilberg O.;Skjold T.;Titlestad I.;Hakulinen A.;Kilpelainen M.;Ben Hayoun M.;Bonniaud P.;Bourdin A.;De Blay F.;Deslee G.;Devouassoux G.;Didier A.;Douadi Y.;Fry S.;Garcia G.;Girodet P. -O.;Leroyer C.;Magnan A.;Mahay G.;Nocent C.;Pison C.;Roux P. -M.;Taille C.;Tiotiu J. -A.;Beck E.;Jandl M.;Kaehler C.;Kassner F.;Koesters F.;Kronsbein J.;Schaum T.;Schulz C.;Skowasch D.;Taube C.;Welte T.;de Roux A.;Beghe Bianca;Blasi F.;Carpagnano G.;Caruso C.;Corsico A. G.;Constantino E.;Crimi N.;Maestrelli P.;Milanese M.;Papi A.;Pelaia G.;Pini L.;Santus P.;Savi E.;Scichilone N.;Senna G.;Spadaro G.;Vaghi A.;Gans S.;Holters J.;Langeveld B.;Pieters W.;Staaks G. H. A.;van Veen I.;van den Berg J. W. K.;Einvik G.;Lehmann S.;Ali Garcia I.;Almonacid C.;Bobolea I.;Campo Mozo P.;de Luiz G.;Domingo Ribas C.;Echave-Sustaeta Maria-Tome J. M.;Garcia Rivero J. L.;Garcia-Cosio Piqueras B.;Gomez-Bastero Fernandez A.;Gonzalez Perez R.;Henriquez Santa A.;Martinez Rivera C.;Munoz Gall X.;Ramos J.;Gregorio Soto Campos J.;Vidal Pan C.;Stenfors N.;Tunsater A.;Vinge I.;Chaudhuri R.;Harrison T.;Mansur A.;Nasser S.;Nordstrom M.;Pfeffer P.;Saralaya D.;Short P.;Adlakha A.;Alpan O.;Averill F.;Badhwar A.;Bardelas J.;Baxter B.;Bensch G.;Berger W.;Bernstein J.;Bridges T.;Brimeyer R.;Calhoun W.;Campbell E.;Cherry W. B.;Chupp G.;Clore L.;Cohn J.;Cole J.;Condemi J.;Cury J.;Davis B.;DeLeon S.;Delacruz L.;Diaz J.;Erb D.;Eziri E.;Fakih F.;Fiedler D.;Fost D.;Fritz S.;Gonzalez E.;Goodman B.;Gottlieb P.;Gottschlich G.;Gower R.;Hajal R.;Harris J.;Heidarian-Raissy H.;Heyder A.;Hill D.;Holguin F.;Hussain I.;Illowite J.;Jacobs J.;Jarratt M.;Kaiser H.;Kao N.;Kashyap R.;Kaufman D.;Kent E.;Kim K.;Klein R.;Kraft M.;Kono R.;Kureishy S.;Leflein J.;Leong M.;Li H.;Lin R.;Lugogo N.;Marcus M.;Maselli Caceres D. J.;Mehta V.;Mello C.;Millard M.;Milstone A.;Moore W.;Moss M.;Mumneh N.;O'Brien T.;Ostransky D.;Palumbo M.;Parikh P.;Parikh S.;Patel A.;Perez G.;Pleskow W.;Prenner B.;Puppala D.;Ramey J.;Reibman J.;Reyes R.;Robinette E.;Rodicio I.;Ryan S.;Sekhsaria S.;Sigal B.;Sikand V.;Soong W.;Spangenthal S.;St. John R.;Steven G.;Subramaniam V.;Sumino K.;Sztejman E.;Tan R. A.;Tanus T.;Thompson C.;Thornblade C.;Villareal M.;Wenzel S.;Zafra H.;Ziedalski T.

2021

Abstract

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p<0·0001) over the 24-week treatment period and provided clinically meaningful and statistically significant improvement from baseline to week 24 in SGRQ total score versus placebo (least squares mean change from baseline −8·11 (95% CI −11·41 to −4·82; p<0·0001), with similar differences at earlier timepoints. Benralizumab improved FEV1, PEF, ACQ-6, CGI-C, PGI-C, PSIA, and SNOT-22 at week 24 versus placebo, with differences observed early (within weeks 1 to 4). Adverse events were reported for 271 (63%) of 427 patients on benralizumab versus 143 (62%) of 229 patients on placebo. The most commonly reported adverse events for the 427 patients receiving benralizumab (frequency >5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

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Scheda completa

Scheda completa (DC)

	Anno di pubblicazione
	
				2021
			
	Rivista
	
				THE LANCET RESPIRATORY MEDICINE
			
	N° del Volume
	
				9
			
	Fascicolo
	
				3
			
	Pagina iniziale
	
				260
			
	Pagina finale
	
				274
			
	Codice DOI
	
				https://dx.doi.org/10.1016/S2213-2600(20)30414-8
			
	Codice WoS
	
				WOS:000631393700028
			
	Codice Scopus
	
				2-s2.0-85099581025
			
	Codice PubMed
	
				33357499
			
	Citazione
	
				Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial / Harrison, T. W.; Chanez, P.; Menzella, F.; Canonica, G. W.; Louis, R.; Cosio, B. G.; Lugogo, N. L.; Mohan, A.; Burden, A.; Mcdermott, L.; Garcia Gil, E.; Zangrilli, J. G.; Pohl, W.; Voves, R.; Deschampheleire, M.; Martinot, J. -B.; Peche, R.; Chapman, K.; Cheema, A.; Dorscheid, D.; Fitzgerald, J. M.; Gagnon, R.; Killorn, W. P.; Olivenstein, R.; Philteos, G.; Ramsey, C.; Rolf, J. D.; Walker, B.; Hilberg, O.; Skjold, T.; Titlestad, I.; Hakulinen, A.; Kilpelainen, M.; Ben Hayoun, M.; Bonniaud, P.; Bourdin, A.; De Blay, F.; Deslee, G.; Devouassoux, G.; Didier, A.; Douadi, Y.; Fry, S.; Garcia, G.; Girodet, P. -O.; Leroyer, C.; Magnan, A.; Mahay, G.; Nocent, C.; Pison, C.; Roux, P. -M.; Taille, C.; Tiotiu, J. -A.; Beck, E.; Jandl, M.; Kaehler, C.; Kassner, F.; Koesters, F.; Kronsbein, J.; Schaum, T.; Schulz, C.; Skowasch, D.; Taube, C.; Welte, T.; de Roux, A.; Beghe, Bianca; Blasi, F.; Carpagnano, G.; Caruso, C.; Corsico, A. G.; Constantino, E.; Crimi, N.; Maestrelli, P.; Milanese, M.; Papi, A.; Pelaia, G.; Pini, L.; Santus, P.; Savi, E.; Scichilone, N.; Senna, G.; Spadaro, G.; Vaghi, A.; Gans, S.; Holters, J.; Langeveld, B.; Pieters, W.; Staaks, G. H. A.; van Veen, I.; van den Berg, J. W. K.; Einvik, G.; Lehmann, S.; Ali Garcia, I.; Almonacid, C.; Bobolea, I.; Campo Mozo, P.; de Luiz, G.; Domingo Ribas, C.; Echave-Sustaeta Maria-Tome, J. M.; Garcia Rivero, J. L.; Garcia-Cosio Piqueras, B.; Gomez-Bastero Fernandez, A.; Gonzalez Perez, R.; Henriquez Santa, A.; Martinez Rivera, C.; Munoz Gall, X.; Ramos, J.; Gregorio Soto Campos, J.; Vidal Pan, C.; Stenfors, N.; Tunsater, A.; Vinge, I.; Chaudhuri, R.; Harrison, T.; Mansur, A.; Nasser, S.; Nordstrom, M.; Pfeffer, P.; Saralaya, D.; Short, P.; Adlakha, A.; Alpan, O.; Averill, F.; Badhwar, A.; Bardelas, J.; Baxter, B.; Bensch, G.; Berger, W.; Bernstein, J.; Bridges, T.; Brimeyer, R.; Calhoun, W.; Campbell, E.; Cherry, W. B.; Chupp, G.; Clore, L.; Cohn, J.; Cole, J.; Condemi, J.; Cury, J.; Davis, B.; Deleon, S.; Delacruz, L.; Diaz, J.; Erb, D.; Eziri, E.; Fakih, F.; Fiedler, D.; Fost, D.; Fritz, S.; Gonzalez, E.; Goodman, B.; Gottlieb, P.; Gottschlich, G.; Gower, R.; Hajal, R.; Harris, J.; Heidarian-Raissy, H.; Heyder, A.; Hill, D.; Holguin, F.; Hussain, I.; Illowite, J.; Jacobs, J.; Jarratt, M.; Kaiser, H.; Kao, N.; Kashyap, R.; Kaufman, D.; Kent, E.; Kim, K.; Klein, R.; Kraft, M.; Kono, R.; Kureishy, S.; Leflein, J.; Leong, M.; Li, H.; Lin, R.; Lugogo, N.; Marcus, M.; Maselli Caceres, D. J.; Mehta, V.; Mello, C.; Millard, M.; Milstone, A.; Moore, W.; Moss, M.; Mumneh, N.; O'Brien, T.; Ostransky, D.; Palumbo, M.; Parikh, P.; Parikh, S.; Patel, A.; Perez, G.; Pleskow, W.; Prenner, B.; Puppala, D.; Ramey, J.; Reibman, J.; Reyes, R.; Robinette, E.; Rodicio, I.; Ryan, S.; Sekhsaria, S.; Sigal, B.; Sikand, V.; Soong, W.; Spangenthal, S.; S, t. John R.; Steven, G.; Subramaniam, V.; Sumino, K.; Sztejman, E.; Tan, R. A.; Tanus, T.; Thompson, C.; Thornblade, C.; Villareal, M.; Wenzel, S.; Zafra, H.; Ziedalski, T.. - In: THE LANCET RESPIRATORY MEDICINE. - ISSN 2213-2600. - 9:3(2021), pp. 260-274. [10.1016/S2213-2600(20)30414-8]
			
	Tutti gli autori
	
						Harrison, T. W.; Chanez, P.; Menzella, F.; Canonica, G. W.; Louis, R.; Cosio, B. G.; Lugogo, N. L.; Mohan, A.; Burden, A.; Mcdermott, L.; Garcia Gil, ...espandi
						
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