Misuri G, Lanini B, Gigliotti F, Iandelli I, Pizzi A, Bertolini M G, Scano G
Fondazione Don C. Gnocchi, ONLUS, Pozzolatico (Firenze), Italy.
Chest. 2000 Feb;117(2):447-53. doi: 10.1378/chest.117.2.447.
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 CO(2) 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.
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.
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.
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. PaCO(2) 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 PaCO(2). Mechanical and breathing pattern variables were introduced in a stepwise multiple regression that selected Eldyn (%Pplsn) (p < 0.0001; r(2) = 0.62) as a unique independent predictor of PaCO(2).
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 CO(2) retention.
在许多针对肌无力患者的研究中，慢性高碳酸血症的严重程度似乎与肌肉疾病的严重程度不成比例，这表明除肌无力外的其他因素也参与了二氧化碳潴留。在慢性阻塞性肺疾病（COPD）患者中，吸气肌负荷与力量的失衡比例被认为会触发综合反应信号，导致呼吸急促、浅快，最终发展为慢性高碳酸血症。尽管这一机制是基于推测，但尚未在肌营养不良患者中得到评估。
连续纳入20例患者（平均年龄47.6岁；范围23至67岁）进行研究：11例肢带型肌营养不良患者、3例杜氏肌营养不良患者、1例夏科-马里-图斯综合征患者、1例贝克型肌营养不良患者、1例强直性肌营养不良患者、1例面肩肱型肌营养不良患者以及2例肌萎缩侧索硬化患者，这些患者均无任何呼吸方面的主诉。选取17例年龄和性别匹配的正常受试者作为对照组。
测量常规肺功能、动脉血气、最大吸气和呼气肌压力（分别为MIP和MEP）以及最大吸气试验时的胸膜压力（Pplsn）。通过评估肺阻力（RL）和动态弹性阻力（Eldyn）来评估肺的力学特性。Eldyn以绝对值和占Pplsn的百分比来评估；Eldyn（%Pplsn）表示每单位吸气肌力的弹性负荷。根据呼吸周期的时间（吸气时间[TI]；呼吸频率[Rf]）和容积（潮气量[VT]）成分来评估呼吸模式。
与对照组相比，研究患者呈现出呼吸急促、浅快的模式，表现为Rf/VT比值更高且TI更低。研究患者的Eldyn更高，而MIP、MEP和Pplsn更低。PaCO₂与VT、TI和Pplsn呈负相关（p分别为0.012、0.019和0.002），而与Rf、Rf/VT、Eldyn和Eldyn（%Pplsn）呈正相关（p < 0.004至p < 0.0001）。此外，Eldyn（%Pplsn）与TI呈负相关，而TI与VT呈正相关。换句话说，Eldyn（%Pplsn）的增加与TI的降低相关，而TI的降低又与更低的VT和更高的PaCO₂相关。将力学和呼吸模式变量纳入逐步多元回归分析，结果选择Eldyn（%Pplsn）（p < 0.0001；r² = 0.62）作为PaCO₂的唯一独立预测因子。
本研究表明，在神经肌肉疾病患者中，弹性负荷和呼吸肌无力是导致呼吸急促、浅快模式并进而引起慢性二氧化碳潴留的原因。
