Valutazione della sicurezza e applicabilità del protocollo Fascial Interventions in Asthmatics Treated with Osteopathy (FIATO) in soggetti con asma severa. Protocollo per uno studio di I Fase

Evaluation of security and applicability of the Fascial Interventions in Asthmatics Treated with Osteopathy (FIATO) in subjects with severe asthma. Protocol for a phase I study

Tesi di: Monzani Elena, Savioli Luca
Relatore: Vismara Luca DO MROI
Correlatori: Dott.ssa Faverio Paola, Dott. Pesci Alberto, Tarantino Andrea DO MROI

2018-2019

Riassunto

INTRODUZIONE
​L’asma è uno dei più comuni disordini respiratori caratterizzato da infiammazione, iper-reattività e ostruzione reversibile delle vie aeree[​ 1]​. Si parla di asma severa quando i sintomi del disturbo non regrediscono nonostante la terapia massimizzata[​ 2]​. Si stima che circa il 3,7% dei pazienti affetti da asma nel mondo,sia classificabile come asma severo[​ 2]​, necessitando anche di terapie biologiche gravate da possibili effetti collaterali e che conducono ad un incremento della spesa pubblica sanitaria[​ 3]​. I protocolli clinici studiati sino ad oggi per verificare l’efficacia della terapia manuale in pazienti asmatici non includono la manipolazione del tessuto connettivo[​ 4]​, nel quale si sviluppano le reazioni infiammatorie[​ 5]​.
Considerando, inoltre, il coinvolgimento del Sistema Nervoso Autonomo (SNA) nella modulazione delle patologie infiammatorie[​ 6]​, ed evidenziando gli effetti del trattamento osteopatico sia sul SNA[​ 7-8] che sul connettivo[​ 9]​, l’obiettivo dello studio è quello di sondare, prima ancora dell’efficacia, la sicurezza del protocollo FIATO in soggetti affetti da asma severa.

METODI
Studio di I fase quasi-sperimentale non-randomizzato, open label, monocentrico, multi-dose, effettuato in 6 soggetti con asma severa stabilizzata mediante terapia massimizzata, includendo farmaci biologici da almeno 3 mesi. Ai partecipanti saranno somministrati 4 trattamenti osteopatici schedulati secondo il protocollo. La sicurezza sarà testata a breve termine, a distanza di tre giorni dal trattamento, scegliendo come variabile surrogata il volume espiratorio massimo nel primo secondo (FEV1) ed accettando un range di peggioramento < 10% rispetto al valore baseline. La sicurezza a lungo termine verrà testata, con la stessa modalità, alla fine dei 4 trattamenti, ossia dopo 2 mesi dalla prima valutazione. L’obiettivo secondario sarà valutare la variazione a breve e medio termine dei parametri spirometrici: FEV1 e FVC (capacità vitale forzata); frazione di ossido nitrico esalata (FeNO); qualità della vita mediante questionario SF-36.

DISCUSSIONE
Analizzando risultati contrastanti di studi condotti sull’efficacia della terapia manuale nel trattamento dei pazienti asmatici, si evince la non presa in considerazione del tessuto connettivo[​ 4] – notoriamente in correlazione con cellule pro infiammatorie[​ 5] e SNA[​ 7-8].​ Si palesa la necessità di sviluppare un protocollo di studio includendo tecniche che ricreino la massima compliance del sistema connettivale, accertandone dapprima la sicurezza per procedere successivamente con lo sviluppo di un trial di fase II.

REFERENZE
1)  Nasreen S, Nessa A, Islam F et al. Changes of peak expiratory flow rate in adult Asthmatic patient. Mymensingh Med J. 2018; 27(2):245-250.

2)  Global Initiative for Asthma. Global Strategy for Asthma Management and prevention, 2019. Available from: ​http://www.ginasthma.org/

3)  Puig-Junoy J, Pascual-Argenté N. Socioeconomic Costs of Asthma in the European Union, United States and Canada: A Systematic Review.​ ​Rev Esp Salud Publica​ 2017; 91​. pii: e201703025.

4)  Hondras MA, Linde K, Jones AP. Manual therapy for asthma (review). Cochrane Database Syst Rev. 2005; (2):CD001002.

5)  Pastwinska J, Agier J, Dastych J et al. Mast cells as the strength of the inflammatory process. Pol J Pathol. 2017; 68(3):187-196.

6)  Benias PC, Wells RG, Sackey-Aboagye B et al. Structure and distribution of an unrecognized interstitium in human tissue. Sci Rep. 2018; 8(1):4947.

7)  Cicchitti L, Martelli M, Cerritelli F. Chronic inflammatory disease and Osteopathy: a systematic Review. PLoS One. 2015; 10(3):e0121327.

8)  Ruffini N, D’Alessandro G, Mariani N et al. Variations of high frequency parameter of heart rate variability following osteopathic manipulative treatment in healthy subjects compared to control group and sham therapy: randomized control trial. Front Neurosci. 2015; 9:272

9)  Tozzi P. Selected fascial aspects of osteopathic practice. J Bodyw Mov Ther. 2012; 16(4):503-19.

Abstract

INTRODUCTION
​Asthma is one of the most common respiratory disorders. Its features are inflammation, hyper-reactivity and obstruction of the airways[​ 1]​. Asthma is defined as “severe” when the symptoms don’t regress despite the maximized cortisone therapy[​ 2]​. It is estimated that in the world about 3,7% of asthmatic patients are afflicted with severe asthma[​ 2]​, for which they need biological therapies that lead to an increase of the public health expenditure and moreover can be burdened with possible side effects[​ 3]​. Clinical protocols that have been studied to verify the efficacy of the manual therapy in asthmatic patients don’t include manipulation of the connective tissue[​ 4] where inflammatory reactions are developed[​ 5]​. Considering the influence of the Autonomic Nervous System (ANS) in the regulation of inflammatory diseases[​ 6] and the osteopathic treatment’s effects on ANS[​ 7-8]​ and on fascial-connective system[​ 9]​, this study has the objective to enquire the security of FIATO protocol in subjects afflicted with severe asthma, and then to probe its efficacy.

METHODS
Quasi – experimental non-randomized Phase I study, open label, monocentric, multi-dose, in 6 patients with severe asthma stabilized for at least three months with a maximized therapy, which includes biological medicines. 4 osteopathic treatments timed according to the protocol will be given to participants. Security will be tested in short term, three days after the treatment, choosing as surrogate variable expiratory volume in the first second (FEV1) and accepting a worsening range of <10% compared to baseline value. Long term security will be proved, in the same way, at the end of 4 treatments, that is 2 months after the first evaluation. The secondary goal will be to appreciate changes in short and medium term of the following spirometric parameters: FEV1 and FVC (forced vital capacity); FeNO (fractional exhaled nitric oxide); quality of life measured with SF-36 questionnaire.

DISCUSSION
​Analyzing conflicting results about studies led to probe manual therapies efficacy in asthmatic patients, an insufficient consideration of connective tissue[​ 4] – notoriously correlated with inflammatory cells[​ 5] and ANS[​ 7-8] – can be deduced. It’s noted the necessity to develop a study protocol that includes techniques directed to investigate the maximum compliance of connective system. Therefore, this protocol is designed to verify the security of FIATO protocol to successively continue with a phase II trial.

REFERENCES
1)  Nasreen S, Nessa A, Islam F et al. Changes of peak expiratory flow rate in adult Asthmatic patient. Mymensingh Med J. 2018; 27(2):245-250.

2)  Global Initiative for Asthma. Global Strategy for Asthma Management and prevention, 2019. Available from: ​http://www.ginasthma.org/

3)  Puig-Junoy J, Pascual-Argenté N. Socioeconomic Costs of Asthma in the European Union, United States and Canada: A Systematic Review.​ ​Rev Esp Salud Publica​ 2017; 91​. pii: e201703025.

4)  Hondras MA, Linde K, Jones AP. Manual therapy for asthma (review). Cochrane Database Syst Rev. 2005; (2):CD001002.

5)  Pastwinska J, Agier J, Dastych J et al. Mast cells as the strength of the inflammatory process. Pol J Pathol. 2017; 68(3):187-196.

6)  Benias PC, Wells RG, Sackey-Aboagye B et al. Structure and distribution of an unrecognized interstitium in human tissue. Sci Rep. 2018; 8(1):4947.

7)  Cicchitti L, Martelli M, Cerritelli F. Chronic inflammatory disease and Osteopathy: a systematic Review. PLoS One. 2015; 10(3):e0121327.

8)  Ruffini N, D’Alessandro G, Mariani N et al. Variations of high frequency parameter of heart rate variability following osteopathic manipulative treatment in healthy subjects compared to control group and sham therapy: randomized control trial. Front Neurosci. 2015; 9:272

9)  Tozzi P. Selected fascial aspects of osteopathic practice. J Bodyw Mov Ther. 2012; 16(4):503-19.