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1. Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study

Author

Menzies-Gow, A., Gurnell, M., Heaney, L. G., Corren, J., Bel, E. H., Maspero, J., Harrison, T., Jackson, D. J., Price, D., Lugogo, N., Kreindler, J., Burden, A., de Giorgio-Miller, A., Faison, S., Padilla, K., Martin, U. J., Gil, E. G., Ardusso, L., Bazerque, R. F., Doreski, P. A. C., Elias, P. C., Gattolin, G., Medina, A. C., Ruiz, X. B., Salvado, A., Del Olmo Sansone, R. A., Wehbe, L., Verra, F. J. B., Brusselle, G., Pilette, C., Martinot, J. -B., Antila, M. A., Blanco, D. C., Cerci, A., Cunha, T. M., Fiss, E., Franza, L., Machado, A. S., De Mattos, W. L. L. D., Grava, S., Minamoto, S. E. T., De Oliveira, C. A., Cheema, A. S., Dorscheid, D., Fera, T. A. E., Gagnon, R., Philteos, G., Sussman, G., Yang, W. H. -C., Aguilar, C. D., Jaller, R., Jazime, M. L., Serrano, F. O., Vanegas, A. C., Vargas, L. K., Villegas, M. F., Hilberg, O., Nielsen, H. B., Nielsen, J., Weinreich, U. M., Ulrik, C. S., Adam, S. M., Deslee, G., Pegliasco, H., Pradelli, J., Roux, P. -M., Russier, M., Deckelmann, R., Eich, A., Forster, A., Herth, F., Kirschner, J., Kirsten, A. -M., Schuhmann, M., Schultz, T. K., Ludwig-Sengpiel, A., Teber, I., Zimmermann, G. S., Almerigogna, F., Celi, A., Paggiaro, P., D'Amato, M., Palange, P., Pirina, P., Spanevello, A., Colin, D. D. H., Hernandez, A. R., Garcia, E. A. R., Gonzalez, E. M., Terrones, R. A. R., Javier, R. C., Suarez, J. F. R., Cheimihska, M., Cudzik, K., Olech-Cudzik, A., Filipek, K., Golinski, L., Kwasniewski, A., Madra-Rogacka, D., Mroz, R., Nittner-Marszalska, M., Pawlukiewicz, M., Lekarska, P. P., Pioszczuk, A., Springer, E., Swiderska, A., Zurowska-Gebala, M., Emelyanov, A. V., Kurbacheva, O., Odegova, A., Peskov, A., Petrov, D. V., Rubanik, T. V., Vasilev, M., Vershinina, M., Barcala, F. J. G., Blanco, V. R., Fernandez, A. M. P., Fernandez, C. G., Garcia, J. M. I., Munoz, A. V. A., Ramos, C. C., Sanz, C. C., Bjermer, L., Chen, C. -Y., Fang, W. -F., Hang, L. -W., Hsu, J. -Y., Kuo, H. -P., Lee, K. -Y., Shen, S. -Y., Sheu, C. -C., Gore, R., Saralaya, D., Alpizar, S. A., Bansal, S., Ismail, H., Kaelin, T. D., Koura, F., Lee, M. D., Maddipati, V., Malur, A., Mcevoy, C. E., Mehta, H., Mohan, A., Moore, W. C., Krings, J., Pippins, A., Deaton, I., Hmieleski, B., Field, P., Reibman, J., Siri, D. D., Sumino, K., Swenson, C., Tilley, S. L., Villareal, M., Pulmonology, and Pulmonary medicine

Subjects
Pulmonary and Respiratory Medicine, Adrenal Cortex Hormones, Humans, Anti-Asthmatic Agents, Recovery of Function, Asthma, Adrenal Insufficiency
Abstract

BackgroundOral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day−1(median (range) 0.0 (0.0–40.0) mg).MethodsThe maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ∼6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events.Results598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0–40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (–19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports.ConclusionsMost patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function.

Published
2022

2. Persistence of both reversible airway obstruction and higher blood eosinophils may predict lung function decline in severe asthma

Author

Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M. G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M. T., Sabato E., Cagnazzo M. G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M. F., Berra A., Calabrese C., Stanziola A. A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E. A., Scibilia G., Vianello A., Marchi M. R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G. E., Foschino Barbaro M. P., Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., Foschino Barbaro M.P., Sposato, B., Scalese, M., Ricci, A., Rogliani, P., Paggiaro, P., Migliorini, M. G., Di Tomassi, M., Olivieri, C., Perrella, A., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Novelli, F., Latorre, M., Vergura, L., Masieri, S., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., and Et, Al

Subjects
Pulmonary and Respiratory Medicine, severe asthma, medicine.medical_specialty, medicine.drug_class, Severe asthma, Eosinophil, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Gastroenterology, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Bronchodilator, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, severe asthma, salbutamol, Forced Expiratory Volume, medicine, Settore MED/10, Immunology and Allergy, Humans, 030212 general & internal medicine, Blood eosinophil, Lung, Genetics (clinical), Lung function, Bronchodilator Agent, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, salbutamol, bronchodilator agents, eosinophils, forced expiratory volume, humans, lung, airway obstruction, asthma, business.industry, Airway obstruction, medicine.disease, Asthma, Bronchodilator Agents, Airway Obstruction, Eosinophils, 030228 respiratory system, Salbutamol, Blood eosinophils, business, medicine.drug, Human
Abstract

Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p=0.0001, 81.8% [66.1–94.3], p=0.0001, 21[18–23], p=0.045 and 230 cells/µl [80–360], p=0.003). A negative relationship between SABA-induced FEV1% changes and pre-bronchodilator FEV1% (β=−0.551%; p=0.0001) and ACT (β=−0.059; p=0.038) was found. Conversely, post-treatment BE levels were positively related (β=145.565 cells/µl; p=0.003) to FEV1>12% increases. A rising trend of pre-/post-bronchodilator FEV1% in time was observed in RAO− subjects with BE300 cells/µl reaching lower values after more than 36months of step-5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE300 cells/µl [p=0.009]). Conclusion: Persistent SABA-induced FEV1>12%, especially when associated to BE>300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.

Published
2020

4. Higher blood eosinophil levels after omalizumab treatment may be associated with poorer asthma outcomes

Author

Sposato, B, Scalese, M, Milanese, M, Masieri, S, Cavaliere, C, Latorre, M, Scichilone, N, Ricci, A, Cresti, A, Santus, P, Olivieri, C, Perrella, A, Rogliani, P, Paggiaro, P, Migliorini, M. G, Di Tomassi, M, Camiciottoli, G, Maselli, R, Pelaia, G, Busceti, M. T, Sabato, E, Cagnazzo, M. G, Colombo, F, Palumbo, L, Ravazzi, A, Bucca, C, Caiaffa, M. F, Berra, A, Calabrese, C, Stanziola, A. A, Schino, P, Di Gioacchino, M, Cazzola, M, Segreti, A, Pastorello, E. A, Scibilia, G, Vianello, A, Marchi, M. R, Paladini, L, Baglioni, S, Abbritti, M, Almerigogna, F, Matucci, A, Vultaggio, A, Maggi, E, Maestrelli, P, Guarnieri, G, Steinhilber, G, Bonavia, M, Rottoli, P, Bargagli, E, Senna, G, Caminati, M, Macchia, L, Bellia, V, Novelli, F, Vergura, L, Rosati, Y, Folletti, I, Pio, R, Pio, A, Maccari, U, Maggiorelli, C, Scala, R, Vignale, L, Pulerà, N, Carpagnano, G. E, Foschino Barbaro, M. P, The Omalizumab Italian Study Group, Sposato, B, Scalese, M, Milanese, M, Masieri, S., Cavaliere, C, Latorre, M., Scichilone, N., Ricci, A., Cresti, A., Santus, P., Olivieri, C., Perrella, A., Rogliani, P., Paggiaro, P., Sposato, B., Migliorini, M. G., Di Tomassi, M., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Novelli, F., Vergura, L., Scalese, M., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., Cavaliere, C., Sposato B., Scalese M., Milanese M., Masieri S., Cavaliere C., Latorre M., Scichilone N., Ricci A., Cresti A., Santus P., Olivieri C., Perrella A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Novelli F., Vergura L., Rosati Y., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., and Foschino Barbaro M.P.

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Treatment outcome, MEDLINE, Omalizumab, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Immunoglobulin E, eosinophil, Omalizumab, anti-IgE, asthma, Leukocyte Count, Text mining, Forced Expiratory Volume, Internal medicine, Eosinophilia, medicine, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Blood eosinophil, Aged, Retrospective Studies, Asthma, biology, business.industry, Retrospective cohort study, Middle Aged, asthma, Prognosis, medicine.disease, Eosinophils, Treatment Outcome, inflammation, biology.protein, Female, business, medicine.drug
Published
2019

5. Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic, Florence, Italy, February to March 2020

Author

Lagi, F., Piccica, M., Graziani, L., Vellere, I., Botta, A., Tilli, M., Ottino, L., Borchi, B., Pozzi, M., Bartalesi, F., Mencarini, J., Spinicci, M., Zammarchi, L., Pieralli, F., Zagli, G., Nozzoli, C., Romagnoli, S., Bartoloni, A., Campolmi, I., Di Lauria, N., Millotti, G., Basile, G., Meli, M., Rogasi, P. G., Bartolozzi, D., Corsi, P., Mazzetti, M., Farese, A., Bresci, S., Cavallo, A., Trotta, M., Corti, G., Morettini, A., Poggesi, L., de Gaudio, A. R., Peris, A., Fontanari, P., Parronchi, P., Almerigogna, F., Annunziato, F., Liotta, F., Cosmi, L., Vultaggio, A., Matucci, A., Angileri, M., Ipponi, A., Cecchi, M., Benemei, S., Vannucchi, A. M., Matucci Cerinic, Marco, and Turco, L.

Subjects
0301 basic medicine, Male, Author's Correction, Epidemiology, COVID-19, Cohort, Florence, ICU, Italy, SARS-CoV-2, pandemic, Age Distribution, Aged, Betacoronavirus, Cannula, Cohort Studies, Comorbidity, Contact Tracing, Coronavirus Infections, Critical Care, Disease Outbreaks, Female, Humans, Intensive Care Units, Middle Aged, Patient Transfer, Pneumonia, Viral, Respiratory Care Units, Sex Distribution, Treatment Outcome, Coronavirus, Pandemics, Disease, medicine.disease_cause, law.invention, 0302 clinical medicine, law, Pandemic, Medicine, 030212 general & internal medicine, Intensive care unit, Rapid Communication, medicine.medical_specialty, 030106 microbiology, 03 medical and health sciences, Virology, business.industry, Public Health, Environmental and Occupational Health, Outbreak, Tropical disease, medicine.disease, Emergency medicine, business, Contact tracing
Abstract

We analysed the first 84 coronavirus disease (COVID-19) patients hospitalised in an infectious and tropical disease unit in Florence, Italy, over 30 days after the start of the COVID-19 outbreak in Italy. A 12% reduction in the rate of intensive care unit transfer was observed after the implementation of intensity care measures in the regular ward such as increasing the nurse/patient ratio, presence of critical care physicians and using high flow nasal cannulae oxygenation.

Published
2020

6. Higher blood eosinophil levels after omalizumab treatment may be associated with poorer asthma outcomes

Author

Sposato, B., Migliorini, M.G., Di Tomassi, M., Olivieri, C., Perrella, A., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M.T., Sabato, E., Cagnazzo, M.G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M.F., Berra, A., Calabrese, C., Stanziola, A.A., Schino, P., Di Gioacchino, M., Rogliani, P., Cazzola, M., Segreti, A., Pastorello, E.A., Scibilia, G., Vianello, A., Marchi, M.R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Paggiaro, P., Novelli, F., Latorre, M., Vergura, L., Masieri, S., Scalese, M., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulerà, N., Carpagnano, G.E., Foschino Barbaro, M.P., Sposato, Bruno, Scalese, Marco, Milanese, Manlio, Masieri, Simonetta, Cavaliere, Carlo, Latorre, Manuela, Scichilone, Nicola, Ricci, Alberto, Cresti, Alberto, Santus, Pierachille, Olivieri, Carmela, Perrella, Antonio, Rogliani, Paola, and Paggiaro, Pierluigi

Published
2019
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9. Asthma control in severe asthmatics under treatment with omalizumab: A cross-sectional observational study in Italy

Author

Novelli, Federica, Latorre, Matteo, Vergura, Letizia, Caiaffa, Maria Filomena, Camiciottoli, Gianna, Guarnieri, Gabriella, Matucci, Andrea, Macchia, Luigi, Vianello, Andrea, Vultaggio, Alessandra, Celi, Alessandro, Cazzola, Mario, Paggiaro, Pierluigi, Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, Laura, Ravazzi, Aldo, Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Paggiaro, P., Novelli, F., Vergura, L., Novelli F., Latorre M., Vergura L., Caiaffa M.F., Camiciottoli G., Guarnieri G., Matucci A., Macchia L., Vianello A., Vultaggio A., Celi A., Cazzola M., Paggiaro P., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Segreti A., Pastorello E.A., Scibilia G., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Maggi E., Maestrelli P., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Bellia V., Scichilone N., Novelli, F., Latorre, M., Vergura, L., Caiaffa, M. F., Camiciottoli, G., Guarnieri, G., Matucci, A., Macchia, L., Vianello, A., Vultaggio, A., Celi, A., Cazzola, M., Paggiaro, P., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Segreti, A., Pastorello, E. A., Scibilia, G., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Maggi, E., Maestrelli, P., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Bellia, V., and Scichilone, N.

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Exacerbation, Cross-sectional study, Omalizumab, Comorbidity, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Exhaled nitric oxide, Exacerbations, Comorbidities, Asthma, Control, Severity of Illness Index, Internal medicine, Severity of illness, Medicine, Anti-Asthmatic Agent, Humans, Pharmacology (medical), Anti-Asthmatic Agents, Inflammation Mediator, Respiratory Function Test, Aged, Cross-Sectional Studie, business.industry, Biochemistry (medical), Middle Aged, medicine.disease, Respiratory Function Tests, Cross-Sectional Studies, Italy, Physical therapy, Observational study, Female, Inflammation Mediators, Comorbiditie, business, medicine.drug, Human
Abstract

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p

Published
2015

19. New advances on human TH1 and TH2 cells

Author

Romagnani, S., Decarli, M., Piccinni, M. P., Manetti, R., Parronchi, P., D'Elios, M. M., Annunziato, F., Sampognaro, S., Giudizi, M. G., Biagiotti, R., Almerigogna, F., Maggi, E., and Delprete, G. F.

Published
1994

28. Analysis of the B-cell growth-promoting activity of human IL-4, the co-stimulatory assay with anti-immunoglobulin antibodies. Comparison with the B-cell growth-promoting activity of other lymphokines.

Author

Almerigogna, F., Giudizi, M. G., Biagiotti, R., Alessi, A., Defrance, T., Banchereau, J., Ricci, M., and Romagnani, S.

Subjects
*IMMUNOGLOBULINS, *INTERFERONS, *B cells, *BLOOD proteins, *GLOBULINS, *PLASMA cells, *ANTINEOPLASTIC agents, *IMMUNOLOGY
Abstract

Human recombinant interleukin-4 (rIL-4) was assessed for its ability to promote the proliferative response of purified human B cells co-stimulated with submitogenic concentrations of soluble F(ab′)2 fragments of anti-immunoglobulin (Ig) antibodies. The growth-promoting activity of rIL-4 was usually as potent as, or even more potent than, that of recombinant interlcukin-2 (rIL-2), and more potent than that of recombinant interferon-gamma (rIFN-γ). Preincubation with rIL-4 did not cause enhancement of the proliferative response of B cells to the subsequent addition of rIL-4 and anti-IgM antibody. In contrast, the proliferative response of B cells preincubated with anti-IgM antibody and rIL-4 was potentiated by the subsequent addition of rIL-4. The simultaneous addition of rIFN-γ and rIL-2 or rIFN-γ, and rIL-4 had an additive effect in comparison with the response induced by rIL-2 or rIL-4 alone, respectively, whereas simultaneous addition of rIL-2 and rIL-4 induced a response equal or lower than that stimulated by rIL-2 or rIL-4 alone. The addition of rIFN-γ at the beginning of culture or preincubation of B cells with rIFN-γ and anti-IgM antibody potentiated the proliferative response of B cells to the subsequent addition of either rIL-2 or rIL-4. Taken together, these data suggest that rIL-4 acts as a growth factor for activated human B cells and displays on such cells a growth-promoting activity similar to that of rIL-2. [ABSTRACT FROM AUTHOR]

Published
1989

30. Direct induction of human B-cell differentiation by recombinant interleukin-2.

Author

Romagnani, S., Del Prete, G., Giudizi, Maria O., Biagiotti, Roberta, Almerigogna, F., Tiri, A., Alessi, Anna, Mazzetti, M., and Ricci, M.

Subjects
INTERLEUKINS, B cell differentiation, INTERLEUKIN-2, B cells, CELL differentiation, CELL culture
Abstract

Recombinant interleukin-2 (rIL-2) induced highly purified human tonsillar B cells to differentiate into immunoglobulin (Ig)-producing cells in vitro. The B-cell response was not due to rIL-2- contaminating substances, but reflected the activity of IL-2 itself, since it was inhibited by addition to the cultures of anti-TAC monoclonal antibody. The rIL-2-induced B-cell response was apparently not mediated by factors released by residual T cells present in B-cell suspensions at undetectable levels, since supernatants (SN) from unstimulated autologous T cells cultured at concentrations even much higher than those possibly contaminating B-cell suspensions did not induce any detectable Ig production. In addition, the Ig production by B cells cultured with SN prepared from high numbers of autologous T cells stimulated with rIL-2, as well as from allo-activated or mitogen-stimulated T cells, was of the same magnitude as the Ig production resulting from direct addition of rIL-2 concentrations comparable with those present in the supernatants. After centrifugation on Percoll density gradients, most of the tonsillar B cells responsive to rIL-2 were recovered in the lower density cell fraction containing a number of larger activated B cells. Moreover, B-cell enriched suspensions from peripheral blood (PB) (which usually contains a lower number of in vivo activated B cells than tonsil) showed poor or no response to rIL-2 alone, but displayed significant Ig production when rIL-2 was added to the cultures in the presence of Staphylococcus aureus Cowan I (SAC) bacteria. Taken together, these data indicate that IL-2 can directly induce differentiation into Ig-producing cells of in vivo or in vitro activated human B cells. [ABSTRACT FROM AUTHOR]

Published
1986

31. Protein A of <em>Staphylococcus aureus</em> is mitogenic for IgG-bearing, but also for a subpopulation of IgM- and/or IgD-bearing human lymphocytes.

Author

Romagnani, S., Giudizi, Grazia M., Almerigogna, F., Nicoletti, P. L., and Ricci, M.

Subjects
STAPHYLOCOCCUS aureus, LYMPHOCYTES, PROTEINS, TONSILS, ERYTHROCYTES, SEPHAROSE, CELL culture
Abstract

The nature of lymphocyte subsets activated by soluble and insoluble protein A (SpA) was investigated by testing the ability of human tonsil populations to form rosettes with human red blood cells coated with SpA (SpA-HRBC) and to respond in vitro to SpA. SpA coupled to Sepharose beads (SpA-Seph) and Staphylococcus aureus strain Cowan I (StaCw). Purified human I cells, which were unable to form rosettes with SpA-HRBC, were not activated by SpA-Seph or StaCw, whereas 8-cell enriched suspensions, where the number of lymphocytes forming rosettes with SpA-HRBC was significantly increased in comparison with that found in unfractionated populations, showed DNA synthesis equal to or greater than unseparated lymphocytes. In contrast, soluble SpA was unable to activate highly purified B lymphocytes in 3 day cultures and induced higher DNA synthesis in unseparated than in purified human T cells. Tonsil cell suspensions depleted in cells forming rosettes with SpA-I-IRBC synthesized significantly less DNA in the presence of SpA-Seph and lost the ability to respond to StaCw. The depletion in either IgG-bearing or IgM- and/or IgD-bearing cells induced a reduction in the response of lymphocytes to SpA-Seph and StaCw. Depletion in IgM- and/or IgD-bearing cells induced a more marked decrease in the response to StaCw than depletion in lgG-bearing lymphocytes, while the decrease of the response to SpA-Seph, induced by depletion in IgM- and/or IgD-bearing cells, was lower than that induced by depletion in lgG-bearing lymphocytes. In contrast, soluble SpA-induced proliferation was not significantly affected by depletion of cells forming rosettes with SpA-HRBC' or of IgG-bearing or IgM- and/or IgD-bearing lymphocytes. These results suggest that the mitogenicity of SpA-Seph and StaCw is due to a selective binding of insoluble SpA to components present on the membrane of either IgO- bearing or IgM- and/or IgD-bearing lymphocytes. They also indicate that the potentiation of T-cell response to soluble SpA, induced by the presence in culture of non-T cells, is not due to B lymphocytes which are able to form ,rosettes with SpA-HRBC and to respond to SpA itself when it is presented to the cells on an insoluble matrix. [ABSTRACT FROM AUTHOR]

Published
1980

32. Protein A Reactivity of Lymphocytes from Some Patients with Chronic Lymphocytic Leukaemia Mediated by an Interaction with the F(ab′)2 Region of Surface Immunoglobulin.

Author

Romagnani, S., Giudizi, M. G., Biagiotti, R., Almerigogna, F., del Prete, G. F., Maggi, E., and Ricci, M.

Subjects
LYMPHOCYTES, BLOOD, LYMPHOCYTIC leukemia, ERYTHROCYTES, STAPHYLOCOCCAL protein A, IMMUNOGLOBULINS, B cells
Abstract

Peripheral blood lymphocytes (PBL) from 15 of 38 patients with chronic lymphocytic leukaemia (CLL) were capable of forming rosettes with human erythrocytes coated with staphylococcal protein A (SpA-HRBC). PBE from seven patients also showed a marked proliferative response after stimulation with Staphylococcus aureus bacteria strain Cowan I (Cowan Staph). The SpA-rosetting of CLL cells was inhibited by incubation with F(ab')2 fragments of anti-immunoglobulin (Ig) antibodies. In addition, incubation with these fragments inhibited the proliferative response of leukaemic B cells to Cowan Staph. The Cowan-Staph-induced proliferation of CLL cells was also impaired by the addition of normal human IgG and human IgG F(ab')2 fragments to the cultures, whereas non-immune rabbit IgG was not inhibitory. The inhibitory activity of human IgG (ab')2 fragments was retained by a SpA-Sepharose column, and it was found in the material recovered from the same column by acid elution. These data indicate that an interaction between SpA and a structure located in the F(ab')2 region of surface Ig of different classes is responsible for either SpA-binding or the Cowan-Staph-induced proliferative response of PBL from some patients with CLL. [ABSTRACT FROM AUTHOR]

Published
1982
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33. Abnormalities of in vitro immunoglobulin production in apparently healthy haemophiliacs: relationship with alterations of T cell subsets and with HTLV-III seropositivity.

Author

Biagiotti, R., Giudizi, M. G., Almerigogna, F., Mazzetti, M., Alessi, A., del Prete, G. F., Rafanelli, D., Fiorilli, M., Morfini, M., and Romagnani, S.

Subjects
IMMUNOGLOBULIN G, MITOGENS, LECTINS, IMMUNOGLOBULINS, HEMAGGLUTININ, PLASMA cells
Abstract

The pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production by cultures of peripheral blood mononuclear cells (PBMC) was reduced in healthy haemophiliacs treated with commercial factor VIII (or IX) concentrate, whereas the spontaneous IgG synthesis in vitro was enhanced, PWM-induced Ig production was lower in those who had received greater amounts of concentrate, in those with inverted T4/T8 lymphocyte ratios and in those with antibody to HTLV-III, The spontaneous IgG production in vitro was higher in haemophiliacs who had received larger amounts of concentrate, in those with inverted T4/T8 ratio and in those with antibody anti-HTLV-III. However, some patients with normal T4/T8 ratio and some with HTLV-III antibody also had raised spontaneous IgG production. [ABSTRACT FROM AUTHOR]

Published
1986

34. In vitro production of IgE by human peripheral blood mononuclear cells II. CELLS INVOLVED IN THE SPONTANEOUS IgE PRODUCTION IN ATOPIC PATIENTS.

Author

Romagnani, S., Del Prete, G. F., Maggi, E., Troncone, R., Giudizi, Grazia M., Almerigogna, F., and Ricci, M.

Subjects
MONONUCLEOSIS, LYMPHOCYTES, T cells, LEUCOCYTES, PLASMA cells, LYMPHOID tissue
Abstract

Spontaneous IgE production in vitro was investigated in 7-day cultures of unfractionated mononuclear cells (MNC) and MNC subpopulations from atopic patients. Depletion of either phagoctytic or adherent cells decreased the amount of IgE detectable in 7-day culture supernatants, but this decrease was due, at least in part, to a loss of cytophilic IgE. Depletion of immunoglobulin-bearing cells (SIg+) reduced significantly but did not abolish the spontaneous IgE production in vitro. On the other hand, depletion of IgM- bearing lymphocytes (SIgM+) which virtually abolished the production of immunoglobulins of the IgM class, did not change significantly the spontaneous production of IgE. Similarly, no change in the spontaneous production of IgE was found when lymphocyte suspensions were depleted of complement receptor-bearing cells (CR+). In contrast. spontaneous IgE product ion was significantly increased by depict ion of T lymphocytes and this increase did not simply reflect the enrichment for IgE-producing cells caused by the fractionation procedure. No significant change in the spontaneous IgE production was found when small numbers of autologous T lymphocytes were added to B cell fractions, whereas the addition of higher concentrations of autologous T cells induced a marked inhibition of the spontaneous IgE production. On the other hand, the addition in culture of pokeweed mitogen (PWM) resulted in a marked reduction of the spontaneous IgE production by B cells, also in the presence of small concentrations autologous T lymphocytes. Normal T cells were consistently effective in inducing a partial inhibition of the spontaneous IgE production by B cells from atopic patients. whereas T cells from a noticeable proportion of atopic patients were not. These data suggest that MNC responsible for the spontaneous IgE production in atopic subjects arc SIgM- and CR-deficient well-differentiated lymphocytes which probably represent the result of an activation which has occurred in vivo. However, this spontaneous IgE production can still be influenced by in vitro manipulation. such as variations in T-B cell ratios or addition of PWM. The results here reported also indicate that normal T cells arc generally more effective than T cells from atopic patients in regulating the activity of spontaneous IgE-producing cells present in the blood of atopic subjects. [ABSTRACT FROM AUTHOR]

Published
1980

35. Activation of human basophils by Staphylococcus aureus Cowan I. II. Alternative F(ab′)-mediated mechanism.

Author

Marone, G., Tamburini, M., Giudizi, M., Biagiotti, R., Almerigogna, F., and Romagnani, S.

Abstract

We investigated the capacity of Staphylococcus aureus Cowan I (Cowan Staph A) and Staphylococcus aureus Wood 46 (Wood Staph A) to induce histamine release from human basophils in vitro. Cowan Staph A (3 × 10 to 3 × 10/ml), which synthesizes protein A (Staph A), stimulated the release of histamine from basophils, whereas Wood Staph A (3×10 to 3×10/ml), which does not synthesize Staph A, did not induce histamine secretion. Soluble Staph A (10 to 10 μg/ml) also induced histamine secretion from human basophils, Hyperiodination of Staph A, which destroys over 90% of the original Fc reactivity without altering the Fab binding site, did not alter this protein's ability to induce histamine release. The stimulating effect of Staph A was suppressed by preincubation with human polyclonal IgG and a human monoclonal IgM, which have F(ab′)-Staph A reactivity. In contrast, rabbit IgG and a human monoclonal IgM possessing only Fe-Staph A reactivity did not inhibit Staph A activity. Preincubation with Staph A or Cowan Staph A resulted in complete cross-desensitization to a subsequent challenge with homologous and heterologous stimuli. These results indicate that Staph A and Cowan Staph A activate human basophils by interacting with the F(ab′) region of IgE and/or IgG present on the cell surface. [ABSTRACT FROM AUTHOR]

Published
1985
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38. Preferential expression of CD30 by human CD4+T cells producing Th2‐type cytokines

Author

Del Prete, G., De Carli, M., Almerigogna, F., Daniel, G. K., Delios, M. M., Zancuoghi, G., Vinante, F., Pizzolo, G., and Romagnani, S.

Abstract

A large panel of human CD4+T helper (Th) cell clones with established Th1, Th2, or Th0 profiles of cytokine secretion were examined for the expression of CD30, a member of the tumor necrosis factor receptor superfamily. Th1 clones expressed poor or no CD30 mRNA, and showed low or undetectable expression of both membrane and soluble CD30 (sCD30) protein, whereas Th2 clones showed both CD30 mRNA and membrane CD30 and released substantial amounts of sCD30, Th0 clones exhibited an intermediate pattern of CD30 expression and release. When T cells from the same donor were stimulated with three different antigens (purified protein derivative, PPD; Toxocara canisexcretory/secretory antigen, TES; Lalium perennegroup I, Lol p I), production of high concentrations of IFN‐γ, but not expression of CD30 or production of IL‐4 and IL‐5, were observed at any time after stimulation with PPD. In contrast, both CD30 expression and production of IL‐4 and IL‐5. but not of IFN‐γ, were concomitantly detectable in TES‐ and Lol p I‐reactive T cells, suggesting a temporal relationship between CD30 expression and beginning of Th2‐typc cytokine production. Finally, CD4+CD30+T cells specific for Lol p I and inducible to production of Th2‐type cytokines were sorted out from the circulation of grass‐sensitive patients in concomitance with the onset of allergic symptoms during the seasonal exposure to grass pollen. Thus, CD30 expression appears to be associated with the differentiation/activation pathway of human T cells producing Th2‐type cytokines.—Del Prete, G., De Carli, M., Almerigogna, F., Daniel, C. K., D'Elios, M. M., Zancuoghi, G., Virante, F., Pizzolo, G., Romagnani, S. Preferential expression of CD30 by human CD4+T cells producing Th2‐type cytokines, FASEB J.9, 81‐86 (1995)

Published
1995
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40. Mechanism of activation of human basophils by Staphylococcus aureus Cowan 1

Author

Marone, G, Tamburini, M, Giudizi, M G, Biagiotti, R, Almerigogna, F, and Romagnani, S

Abstract

We investigated the capacity of Staphylococcus aureus Cowan 1 and S. aureus Wood 46 to induce histamine release from human basophils in vitro. S. aureus Cowan 1 (10(5) to 10(7)/ml), which synthesizes protein A (Staph A), stimulated the release of histamine from basophils, whereas S. aureus Wood 46 (10(5) to 2 X 10(7)/ml), which does not synthesize Staph A, did not induce histamine secretion. Soluble Staph A (10(-3) to 10 micrograms/ml), but not staphylococcal enterotoxin A, induced histamine secretion from human basophils. Staph A binds through its classical site to the Fc region of human immunoglobulin G (IgG) and through its alternative site to the Fab portion of the different human immunoglobulins. Hyperiodination of Staph A, which destroys over 90% of the original Fc reactivity without altering the Fab-binding site, did not alter the ability of the protein to induce histamine release. The stimulating effect of Staph A was dose dependently inhibited by preincubation with human polyclonal IgG (0.3 to 100 micrograms/ml) and a human monoclonal IgM (0.3 to 100 micrograms/ml) which have F(ab')-Staph A reactivity. In contrast, rabbit IgG, which possesses only Fc-Staph A reactivity, and a Staph A-unreactive human monoclonal IgM did not inhibit Staph A activity. Similar results were obtained with intact S. aureus Cowan 1. Preincubation with either Staph A or anti-IgE (rabbit anti-Fc epsilon) resulted in complete desensitization to a subsequent challenge with the homologous stimulus. Staph A and anti-IgE induced partial cross-densensitization to the heterologous stimulus. Cells preincubated with anti-IgG (rabbit anti-Fc gamma) lost a small but significant part of their ability to release with Staph A but did not lose their response to anti-IgE. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and Staph A. When basophils from which IgE had been dissociated were incubated with human polyclonal IgE, they regained their ability to induce histamine in response to Staph A and anti-IgE. In contrast, two monoclonal IgEs which do not bind to Staph A did not restore the basophil responsiveness to Staph A. Furthermore, there was complete cross-desensitization between soluble Staph A and S. aureus Cowan 1, while cells desensitized to S. aureus Wood 46 released normally with Staph A and S. aureus Cowan 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Published
1987
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42. Analysis of the B-cell growth-promoting activity of human IL-4, the co-stimulatory assay with anti-immunoglobulin antibodies. Comparison with the B-cell growth-promoting activity of other lymphokines

Author

Almerigogna F, Mg, Giudizi, Biagiotti R, Alessi A, Thierry DEFRANCE, Banchereau J, Ricci M, and Romagnani S

Subjects
B-Lymphocytes, Interleukins, Palatine Tonsil, hemic and immune systems, chemical and pharmacologic phenomena, Immunoglobulin D, Lymphocyte Activation, biological factors, Recombinant Proteins, Antibodies, Anti-Idiotypic, Interferon-gamma, Adjuvants, Immunologic, Immunoglobulin M, parasitic diseases, Humans, Interleukin-2, Interleukin-4, Child, Cells, Cultured, Research Article
Abstract

Human recombinant interleukin-4 (rIL-4) was assessed for its ability to promote the proliferative response of purified human B cells co-stimulated with submitogenic concentrations of soluble F(ab')2 fragments of anti-immunoglobulin (Ig) antibodies. The growth-promoting activity of rIL-4 was usually as potent as, or even more potent than, that of recombinant interleukin-2 (rIL-2), and more potent than that of recombinant interferon-gamma (rIFN-gamma). Preincubation with rIL-4 did not cause enhancement of the proliferative response of B cells to the subsequent addition of rIL-4 and anti-IgM antibody. In contrast, the proliferative response of B cells preincubated with anti-IgM antibody and rIL-4 was potentiated by the subsequent addition of rIL-4. The simultaneous addition of rIFN-gamma and rIL-2 or rIFN-gamma and rIL-4 had an additive effect in comparison with the response induced by rIL-2 or rIL-4 alone, respectively, whereas simultaneous addition of rIL-2 and rIL-4 induced a response equal or lower than that stimulated by rIL-2 or rIL-4 alone. The addition of rIFN-gamma at the beginning of culture or preincubation of B cells with rIFN-gamma and anti-IgM antibody potentiated the proliferative response of B cells to the subsequent addition of either rIL-2 or rIL-4. Taken together, these data suggest that rIL-4 acts as a growth factor for activated human B cells and displays on such cells a growth-promoting activity similar to that of rIL-2.

Published
1989

43. In vitro production of IgE by human peripheral blood mononuclear cells. IV. Modulation by allergen of the spontaneous IgE antibody biosynthesis

Author

Romagnani, S, Maggi, E, Del Prete, G F, Almerigogna, F, Biagiotti, R, Giudizi, M G, and Ricci, M

Subjects
Time Factors, Antibody Specificity, T-Lymphocytes, otorhinolaryngologic diseases, food and beverages, Humans, Pollen, Rhinitis, Allergic, Seasonal, DNA, Lymphocytes, Immunoglobulin E, Cells, Cultured, Research Article
Abstract

Peripheral blood lymphocytes (PBL) from a proportion of grass-sensitive patients, studied during or immediately after the grass pollination period, showed spontaneous production in vitro of grass-specific IgE antibody, whereas PBL from atopic patients sensitive to allergens other than grass pollens or non-atopic individuals did not. Pre-incubation of IgE antibody producing PBL from grass-sensitive patients with minute amounts of a mixed grass pollen (MGP) extract or Rye grass antigen Group I (Rye I) usually resulted in a reduction of the spontaneous production in vitro of IgE protein and in a marked inhibition of the spontaneous production in vitro of grass-specific IgE antibody. This antigen-specific inhibition was not mediated by T lymphocytes, but it was apparently due to a signal directly delivered by antigen to the spontaneously IgE antibody producing cells. The results support the concept that the activity of cells responsible for the persistent IgE antibody formation in vitro in atopic patients can be modulated by antigen.

Published
1982

44. The pathology of Omenn's syndrome

Author

Chilosi, M., Fabio FACCHETTI, Notarangelo, L. D., Romagnani, S., Del Prete, G., Almerigogna, F., and Carli, M.

Subjects
Child, Histiocytic Sarcoma, Humans, Immunohistochemistry, Immunophenotyping, Ki-1 Antigen, Lymph Nodes, Skin

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