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Clinical Investigations: CONTROL OF BREATHING |

Mechanism of CO2 Retention in Patients With Neuromuscular Disease*

Gianni Misuri, MD; Barbara Lanini, MD; Francesco Gigliotti, MD; Iacopo Iandelli, MD; Assunta Pizzi, MD; Maria Grazia Bertolini, RT; Giorgio Scano, MD, FCCP
Author and Funding Information

*From the Fondazione Don C. Gnocchi, ONLUS, Pozzolatico (Firenze), Italy. This study was supported by a grant from MPI of Italy.

Correspondence to: Giorgio Scano, MD, FCCP, Section of Respiratory Disease, Fondazione Don C. Gnocchi, ONLUS, Pozzolatico, Via Imprunetana, Pozzolatico (Firenze), CAP 50020 Italy; e-mail: riabrfi@tin.it



Chest. 2000;117(2):447-453. doi:10.1378/chest.117.2.447
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Background: In many studies of patients with muscle weakness, chronic hypercapnia has appeared to be out of proportion to the severity of muscle disease, indicating that factors other than muscle weakness are involved in CO2 retention. In patients with COPD, the unbalanced inspiratory muscle loading-to-strength ratio is thought to trigger the signal for the integrated response that leads to rapid and shallow breathing and eventually to chronic hypercapnia. This mechanism, although postulated, has not yet been assessed in patients with muscular dystrophy.

Subjects: Twenty consecutive patients (mean age, 47.6 years; range, 23 to 67 years) were studied: 11 patients with limb-girdle dystrophy, 3 with Duchenne muscular dystrophy, 1 with Charcot-Marie-Tooth syndrome, 1 with Becker muscular dystrophy, 1 with myotonic dystrophy, 1 with facioscapulohumeral dystrophy, and 2 with amyotrophic lateral sclerosis, without any respiratory complaints. Seventeen normal subjects matched for age and sex were studied as a control group.

Methods: Routine spirometry and arterial blood gases, maximal inspiratory and expiratory muscle pressures (MIP and MEP, respectively), and pleural pressure during maximal sniff test (Pplsn), were measured. Mechanical characteristics of the lung were assessed by evaluating lung resistance (RL) and dynamic elastance (Eldyn). Eldyn was assessed as absolute value and as percent of Pplsn; Eldyn (%Pplsn) indicates the elastic load per unit of inspiratory muscle force. Breathing pattern was assessed in terms of time (inspiratory time [Ti]; respiratory frequency [Rf]) and volume (tidal volume [Vt]) components of the respiratory cycle.

Results: A rapid shallow breathing pattern, as indicated by a greater Rf/Vt ratio and a lower Ti, was found in study patients compared to control subjects. Eldyn was greater in study patients, while MIP, MEP, and Pplsn were lower. Paco2 inversely related to Vt, Ti, and Pplsn (p = 0.012, p = 0.019, and p = 0.002, respectively), whereas it was directly related to Rf, Rf/Vt, Eldyn, and Eldyn (%Pplsn) (p < 0.004 to p < 0.0001). Also Eldyn (%Pplsn) inversely related to Ti, and the latter positively related to Vt. In other words, increase in Eldyn (%Pplsn) was associated with decrease in Ti, and the latter was associated with lower Vt and greater Paco2. Mechanical and breathing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r2 = 0.62) as a unique independent predictor of Paco2.

Conclusions: The present study shows that in patients with neuromuscular disease, elastic load and respiratory muscle weakness are responsible for a rapid and shallow breathing pattern leading to chronic CO2 retention.

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