Eur Respir J 1989. 2. 846--852. Total respiratory resistance and reactance in patients with diffuse interstitial lung disease J.A. van Noord, J. Clement, M. Cauberghs, I. Martens, K.P. Van de Woestijne, M. Demedts Total respiratory resisJance an.d reactance in patients with diffuse interstitial Dept of Pathophysiology, Laboratory of Pnewnology, lung disease. J .A. van Noord, J. Clement, M. Cauberghs, /. Mer tens, Catholic University, Leuven, Belgiwn. K.P. Van de Woesrijne. M. Demedts. ABSTRACT: In 54 patients with In terstitial lung diseases and no signs of airway obstruction we measured lung volumes, maximal expiratory flows, Correspondence: M. Demedts, Kliniek voor diffusing capacity (DLco), total respiratory resistance (Rrs) and reactance Longziekten, UniversitaiT Zienkenhuis, Weligerveld (Xrs) between 4 and 26 Hz by means of the forced osclllaticm technique. I, B-3041 Pellenbcrg, Belg ium. l n all patients D LCO was less than 75% of the expected val ue. Patients were classified Into two groups depending on total lung capacity (TLC): group A wi th TLC less than 80% of expected, and group n with TLC of 80% or more. Group A demonstrated a decrease of Xrs especlaLJy at low Keywords: Forced oscillation technique; interstitial frequencies, with small, not significant changes In Rrs. ln Lite patients In lung disease; respiratory impedance; respiratory tbls group with the lowest values of TLC (less than 50%), we observed an mechanics. Increase of Rrs at low frequencies causing a negative frequency dependence of Rrs. In group B no distinct changes of Rrs and Xrs occurred. Canonical correlation analysis between routine lung function Received: 4 October 1988; accepted after revision 16 data and forced oscillation parameters, showed tight correlations between May 1989. TLC ln absolute value or VC In percent of the predicted value on the one band and average level of Xrs and average slope of Xrs (and Rrs) vs frequency cur ves on the other hand. Measurements of lung mechanics In five additional patients and compar iso n with a model of the respiratory This study was supponed by a grant from the system suggest that the changes of Rrs and Xrs are not explajned totally Netherlands Asthma Fonds, the Fonds voor Geneeskundig Wetenschappelijk Onder.wek and the by the observed Increase In lung tissue resistance and decrease ln lung European Community for Coal and Steel. compliance. The observed changes ln Rrs and Xrs are not speclnc for restrictive lung disorders; similar changes are met also in moderately advanced obstructive diseases. Eur Respir J., 1989, 2, 846-852 The pathophysiologic pattern in patients with diffuse were qualitatively similar to those in patients with chronic interstitial lung disease is well established: lung volumes obstructive lung disease but were less pronounced. and diffusing capacity are reduced, lung elastic recoil is However, detailed studies relating the amount of increased, airway resistance is nonnal, maximal expira­ restriction (indicated by the reduction in 1LC) to the tory tlows adjusted to volume are usually nonnal or high changes of Rrs and Xrs vs frequency curves in although in some patients a narrowing of small airways well-defmed groups of patients have not been perfonned. has been documented, and lung tissue resistance is Therefore, we studied a group of patients with widely increased [1-11]. Very little infonnation exists about the varying degrees of pulmonary restriction due to intersti­ influence of these disturbances in pulmonary mechanics tial lung disease, in order to compare the Rrs and Xrs vs on total respiratory resistance (Rrs) and reactance (Xrs) frequency curves with lung volumes and maximal flows. measured with the forced oscillation technique. SoBOL Also a model analysis was used to explain the observed [12] measured total respiratory impedance at 6 Hz in 15 changes of the curves. patients with restrictive lung disease and found increased values in 60% of them, while correlation between im­ pedance and airway resistance was poor. FrsHER et al. Patients and methods [13] found, in nine patients with diffuse pulmonary diseases, that mean values of Rrs (measured at the reso­ Patients nant frequency) and of the resonant frequency were nonnal, although three patients showed increased values Fifty-four patients, 24 females, and 30 males, with of Rrs. MOLLER and VooEL [14] detennined Rrs and Xrs clinical, radiological, and functional abnormalities between 5 and 30 Hz in 12 patients wilh a restrictive consistent with interstitial lung disease of various defect and concluded that the changes in Rrs and Xrs etiologies were studied. Lung biopsy was perfonned in INTERSTITIAL LUNG DISEASE AND RESPIRATORY IMPEDANCE 847 case diagnosis could not be made on the basis of the Methods clinical data. Patients with a history or functional evidence of chronic obstructive lung disease were ex­ The pulmonary function measurements performed in cluded, and the ratio forced expiratory volume in I s group A and B consisted of static and dynamic lung (FEY 1)/vital capacity (VC) had to be more than 70%. volumes, max imal expiratory now volume curves The diffusing capacity (OLeo) was less than 75% of the (MEFV). diffusing capacity (OLeo), and Rrs and Xrs vs expected value. The patients were classified into group frequency curves. A (n=35) if total lung capacity (TLC) was less than 80% Vital capacity (VC), total lung capacity (TLC). of Lhe expected value, and into group B (n= 19) if TLC functional residual capacity (FRC), residual volume (RV), A ) was more than 80%. Group included 9 pati ents with forced expiratory volume in one second (FEV1 were sarcoidosis, 9 with idiopathic pulmonary fi brosis, 4 wit11 obtained by standard methods of spirometry and exLrinsic allergic alvcolitis, 6 with collagen disease mu 1Libreat11 helium equilibration. Measured values were (without muscular involvement or pleural abnorm alities related to t11e normal values of JoUAssr:r [151. Peak on the chest X-ray), 2 with bleomycin-induced pneumo­ expiratory now (PEF) and maximal now at 50% of the nitis, 2 with .longstanding miLral valve stenosis, 2 witll forced vital capacity (MEF5c) were obtained from MEFV hard metal disease and 1 with silicosis. In group B, 2 curves measured at the moutll and related to the normal patients had idiopathic pulmonary fi brosis, 5 sarcoidosis, values of the ECCS [16]. To obtain MEF50 as a percent­ 9 bleomycin-induced pneumonitis, 2 long standing mitral age of the ex pected value a correcti on for lung volume valve disease and I extrinsic allergic alveolitis. changes was applied: tlle measured MEF was expressed 50 ln fi ve additional male patients wilh restricti ve disease in percentage of Lhe expected llow at the same absolute (TLC: 50-65% of expected) and no signs of airway volume (MEF~ %. Cp ). First. absolute volume was obstruc ti on, pulmonary mechanics were studied. Diagno­ calculated by aoWng '5~% of actual FVC to actual RV. ses included 2 ca<;es of silicosis, 1 of sarcoidosis, I of By subtracting predicted RV (expressed in absolute lymphoid interstitial pneumonitis and 1 of asbestosis values) the percentage of predicted VC witll which this (without pleural involvement). volume corresponds was then derived . Finall y, Table 1. - Results of the pulmonary function tests Group A (n=35) Group B (n=19) p(A-B) Age yrs 44±16 44±16 NS Height cm 168±9 171±11 NS Weight kg 68±16 66±15 NS TLC %expected 63±11 91±11 <0.001 VC %expected 58±15 82±12 <0.001 RV %expected 80±21 118±32 <0.001 FRC{fLC% 57±10 60±8 NS FEVI %expected 62±17 86±12 <0.001 FEY/VC% 80±6 79±5 NS DLCO %expected 58±13 57±11 NS Kco %expected 90±17 65±11 <0.001 PEF %expected 71±21 77±18 NS MEF50 %expected 238±152 93±30 <0.001 Rrs kPa·t1·s 0.29±0.07 0.24±0.06 <0.05 Rrs0 > kPa·t1·s2 -0.061·1 o·~o.265·1 o·2 0.11 · 10"~0.14·10" 2 <0.01 Rrs<2> kPa-t1-s3 0.015·10"2:t0.092·10"2 o.Ot9·I0·2:to.056·t0·2 NS Xrs kPa·t1·s 0.01±0.05 0.07±0.04 <0.001 Xrs<1> kPa·t1·s2 0.013±0.004 O.Oll±{l.003 <0.05 Xrs<2> kPa·t1-s3 -0.13·I0·2:to.o8-to·z -0.13·10"2:t0.05·10"2 NS Values are mean ±so. The third column indicates the statistical differences between group A and B; NS: non­ significant (p>0.05); TLC: total lung capacity; VC: viwl capacity; RV: residual volume; FRC: functional residual capacity; FEY : forced expiratory volume in one second; Dt.co: single breath di[fusing capacity for CO; 1 : Kco: Dt.co over lung volume; PEF: peak expiratory Oow ~le; MEF5 max i.mal expiratory now at 50% of forced vital capacity, corrected for lung volumes (see Method!:); Rrs, Rrs< 1) .~<21 : mean value, first (slope) and second derivatives (curvature) of total respiratory resistance; ~ . XrsO>, xr:~<2>: mean vtl)u cs, (irst and second derivatives of total respiratory reactance. 848 I. A. V AN NOORD ET AL. MEF was Lhen calculated by linear interpolation and Xrs were all measured during tidal breathing at FRC • of Lhe~~~ values of MEF,s. MEF30 and MEF25 Dt.co without previous deep inspirations to 1LC. was obtained with the single brcalh method and related to the reference values of BllllET et al. [17]. Rrs and Xrs were determined by means of a forced Results oscillation technique previously described in detail [18, 19]. Briefly, a pseudo-random noise signal, containing Volumes, maximal flows, diffusing capacity and respi­ all harmonics of 2 Hz up to 26 Hz (2, 4, 6,...