Impulse oscillometry indices to detect an abnormal lung clearance index in childhood cystic fibrosis. Bokov P, 

Gerardin M, Le Clainche L, Houdouin V, Delclaux C. Pediatr Pulmonol​. 2021 Dec; 56(12):3752-7.

The objective of our cross-sectional study was to assess the relationships between indices of multiple breath washout (MBW) and impulse oscillometry system (IOS) in cystic fibrosis in forty consecutive children (median age 8.1 years) in stable conditions and to evaluate whether cut-off values of IOS indices may help to avoid MBW, which is time-consuming. IOS measurements took a median duration of 3 min, while MBW measurements took a median duration of 49 min. Lung Clearance Index (LCI2.5% ) depicted significant linear correlations with z-scores of R5Hz, R5-20Hz, X5Hz, AX, and Fres (r2 = 0.27 to 0.51). Receiver-operator characteristic curves were constructed and showed that the best compromise was obtained with the z-score of Fres, with a cut-off value of -1.37 that had a sensitivity of 0.966, a specificity of 0.636, and a negative predictive value of 0.875. This z-score is useful for excluding increased LCI2.5% when below -1.37 using the reference set of Gochicoa et al. In conclusion, IOS measurement is easily and rapidly obtained in children and may be clinically useful for excluding increased LCI2.5% , thus allowing the time-consuming MBW test to be avoided.

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Is Impulse Oscillometry System a Useful Method for the Evaluation and Follow-Up of Patients with Cystic Fibrosis? Kartal Öztürk G, Eşki A, Gülen F, Demir E. Pediatr Allergy Immunol Pulmonol. 2021; 34(1):15-22.

Background: Although the impulse oscillometry system (IOS) is a noninvasive, easily accessible, well-tolerated, and alternative test, routine use of IOS in cystic fibrosis (CF) patients is not widespread. In our unit, IOS is routinely used for the evaluation and follow-up of patients with CF. We aimed to show that IOS may be utilized as a complement for measuring pulmonary function in CF patients. 

Materials and Methods: Retrospective data collection and analysis of pulmonary function tests on CF patients followed at our center between January 1, 2018 and February 1, 2019. IOS and spirometry data were compared as correlated with patients' clinical exacerbation, treatment response, bronchodilator response, and trends during follow-up intervals. 

Results: There was a significant correlation between spirometry and IOS parameters in 70 patients. In exacerbation, Z5, R5-R10, AX, Fres, and delta R5-R20 were significantly increased and X5-X20 was significantly decreased compared with baseline in 25 patients. After treatment, IOS parameters were observed to return to baseline values. In the evaluation of bronchodilator response in 33 patients, significant changes in IOS (decrease in Z5, R5-R10, AX, Fres, and delta R5-R20, and increase in X5-X10) and in spirometry [increase in forced expiratory volume in 1 s (FEV1) and forced expiratory flow during the middle half of forced vital capacity (FEF25-75)] were found after bronchodilator. While there was no significant difference between spirometry values in follow-up visits in 31 patients, there was a significant increase in Z5% and R5%-R20%. Unlike other studies, there was a significant correlation between clinical scores and IOS. 

Conclusions: These results show that although IOS is not the gold standard method such as spirometry, it is an alternative method that can be used successfully in the evaluation and follow-up of CF patients.

 

Coughing and diaphragmatic breathing exercise: What is the repercussion on respiratory mechanics of children and adolescents with cystic fibrosis? Castilho T, Gonçalves Wamosy RM, Cardoso J, Camila Mucha F, Jandt U, Schivinski CIS. Int J Clin Pract. 2021 Sep 15:e14879.

Introduction: The aim of this study was to investigate the immediate effect of coughing episodes and diaphragmatic breathing exercise (DBE) on respiratory mechanics of children/adolescents with cystic fibrosis (CF).

Methods: It is a cross-sectional analytical study that occurred in a reference center for children with CF. Forty-five children/adolescents with CF (60% male; mean age 10.22 ± 2.84 years old; mean forced expiratory volume in 1 second 73.74 ± 21.38% predicted) were divided into 3 groups according to the R5 parameter response to the DBE: G1 (increased R5), G2 (no change R5), and G3 (decreased R5). The children/adolescents performed 5 successive coughs and 10 DBE. The main outcome measures were the impulse oscillometry system (IOS) parameters evaluated before, during, and after the interventions.

Results: In the total sample, the IOS parameters (Z5, R5, and R20) were worse after coughing, and they did not change after the DBE. In the G1, the parameters were progressively worsening during the interventions. In the G2, they worsened after coughing and after the DBE. In the G3, they worsened after coughing; however, after the DBE, the IOS parameters have improved and returned close to the baseline.

Conclusions: The children/adolescents with CF airway resistance got worse after coughing episodes, and 10 DBE repetitions did not affect the respiratory mechanics in most of the sample. Meanwhile, in the group with older children, the DBE worsened the respiratory mechanics, yet in the younger group it improved.

 

Immediate effect of inhalation therapy combined with oscillatory positive expiratory pressure on the respiratory system of children with cystic fibrosis. Gonçalves Wamosy RM, Castilho T, Almeida ACDS, de Assumpção MS, Ludwig Neto N, Schivinski CIS. Int J Clin Pract. 2021 Oct;75(10):e14659.

Introduction: It is recommended the association of inhalation therapies and physiotherapy on the management of cystic fibrosis (CF); however, it is still necessary to understand the effect on respiratory mechanics of these therapies combined. This study aimed to evaluate the immediate effect of inhalation with Dornase-Alfa (DNase) and hypertonic saline solution (HSS), as well as the impact of these inhalation therapies associated with an oral high-frequency oscillation (OHFO) physiotherapy device, on the respiratory mechanics of children and adolescents with CF.

Method: Children/adolescents with CF were allocated into two groups (DNaseG and HSSG), where they performed inhalation therapy before using the OHFO device for physiotherapy. In each group, the Impulse Oscillometry System was conducted before and after inhalation therapy, and after OHFO. ANOVA was carried out to analyse the respiratory mechanics at different moments of DNaseG and HSSG. The Mann-Whitney test compared the immediate effect of each inhalation therapy and after OHFO.

Results: 30 children (6-14 years old) were studied. In DNaseG, the mean value of most oscillometric parameters decreased in the evaluated moments; in HSSG, only reactance showed an immediate increase.

Conclusion: Children/adolescents with CF showed an immediate decrease in airway resistance and reactance after the use of DNase and associated with OHFO, indicating improvement. The inhalation with HSS has an immediate effect on peripheral airways.

 

Prognosis-Based Early Intervention Strategies to Resolve Exacerbation and Progressive Lung Function Decline in Cystic Fibrosis. Neeraj Vij.  J Pers Med. 2021 Feb 3;11(2):96.

 

Investigating outcome measures for assessing airway clearance techniques in adults with cystic fibrosis: protocol of a single-centre randomised controlled crossover trial. Stanford G, Davies JC, Usmani O, Banya W, Charman S, Jones M, Simmonds NJ, Bilton D. BMJ Open Respir Res. 2020 Oct;7(1):e000694.

Introduction: Airway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT.

Methods and analysis: This is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30-60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64).

 

Impulse oscillometry and spirometry measurements relative to personal best values at the time of acute exacerbations of cystic fibrosis in adults. Blin T, Flament T, Mankikian J, Chambellan A, Marchand-Adam S, Plantier L. Clin Physiol Funct Imaging. 2021 Jan;41(1):76-84.

Background: Diagnosis of acute exacerbation (AE) of cystic fibrosis (CF) must be precise because both under- and over-prescription of antibiotics may be detrimental. How lung function tests contribute to diagnose AE is unclear. We aimed to describe variation of spirometry and oscillometry measurements, at Stable state and at AE in adults with CF.

Methods: Patients were included in a retrospective single-centre study when both spirometry (FEV1, FVC) and oscillometry (X5, R5, R5-R20 & AX) data were available for at least one Stable & one AE visit between December 2016 and July 2019. For each visit, we calculated variation (Δ) in spirometry and oscillometry indices in comparison with personal best values. Measurements were expressed as % of predicted values & Z-scores when applicable. Areas under ROC curves (AUC) were computed.

Results: Forty-two patients (28 ± 9 years, FEV1 64 ± 21%) were included; 80 AE and 104 Stable visits were analysed. FEV1 (L, %pred and Z-score) and FVC (%pred and Z-score) varied significantly between AE and Stable visits (p<.05), although differences were small (80 ml/2.7%pred for FEV1). Among oscillometry indices, X5 (kPa.s.L-1 ),  R5-R20 (kPa.s.L-1 ) and AX (kPa/L) varied significantly. The AUCs for the variation in spirometry indices ranged from 0.601 (ΔFVC L) to 0.635 (ΔFEV1%pred). They were not significantly different from the AUCs for ΔX5 (0.589), ΔR5-R20 (0.649) & ΔAX (0.598).

Conclusions: Performance of both spirometry and oscillometry to discriminate AE from Stable state was poor. Variation of oscillometry indices (X5, R5-R20, AX) may be helpful when spirometry is unreliable or uncomfortable.

 

Reliability of impulse oscillometry parameters in healthy children and in children with cystic fibrosis.

Wamosy RMG, Assumpção MS, Parazzi PLF, Ribeiro JD, Roesler H, Schivinski CIS. Int J Clin Pract. 2021 Apr;75(4):e13715

Introduction & aims: Impulse oscillometry system (IOS) is an instrument developed to evaluate the mechanical lung properties. It has been reported that to analyse the exam in a proper way it is necessary to carry out more than one measure. However, studies addressing the standardisation are still scarce. The objective was to determine within trial reliability of three measures in IOS parameters in healthy children and children with cystic fibrosis (CF).

Method: Weight, height, body mass index, forced spirometric and the oscillometric parameters (resistance, respiratory impedance, respiratory reactance and resonance frequency) data were collected, in a way that all participants performed three IOS measures. To evaluate, the reproducibility was used the intraclass correlation coefficient [two-way mixed model, absolute agreement definition, ICC]. The response stability was appraised using the standard error of measurements (SEM) in three repetitions of the IOS in the healthy children group (HCG) and in the cystic fibrosis group (CFG).

Results: About 95 subjects participated, in each group with a mean age of 10.89 ± 2.21 years old in the HCG and 9.73 ± 2.43 years old in the CFG, having been 41 and 43 boys and 54 and 52 girls, in the respectively group. In both groups, all IOS parameters evaluated in the three measures presented an ICC of 0.9, which is a high reproducibility.

Conclusion: The IOS parameters are reproducible for healthy children and CF children in three measures. However, according to the population studied, the performance of only one measure is sufficient to assess respiratory mechanics, whereas the SEM were low, except for Fres, in both groups.

 

"Reactance inversion" at low frequencies in a child undergoing treatment of a cystic fibrosis exacerbation. Allen JL, Ren CL, McDonough J, Clem CC. Pediatr Investig. 2019 Dec 21;3(4):257-260.

Introduction: Impulse oscillometry (IOS) employs high frequency sinusoidal or impulse pressure and flow waveforms to interrogate the mechanical properties of the respiratory system. It has special applications to preschool and younger children who may have difficulty performing the repetitive forced expiratory maneuvers required for spirometry.

Case presentation: We present a case illustrating improvements of respiratory system mechanics measured by IOS in a 6-year-old child with cystic fibrosis (CF) who demonstrated clinical and radiological improvement after a course of therapy with hospitalization and intravenous antibiotics, and initiation of a cystic fibrosis transmembrane regulator (CFTR) protein corrector/potentiator agent. We also report a new finding: observed lower than expected reactance at low compared to high frequencies ("reactance inversion").

Conclusion: Reactance inversion may reflect parallel pathway inhomogeneities in resistance and elastance or intrabreath airway inertance changes in young children with CF. Further study is needed in children with airway obstruction due to asthma, cystic fibrosis, and chronic lung disease of infancy to demonstrate the prevalence of this finding and whether it is specific to a measurement device.

 

Pediatric Glittre ADL-test in cystic fibrosis: Physiological parameters and respiratory mechanics. Almeida AC, Wamosy RMG, Ludwig Neto N, Mucha FC, Schivinski CIS. Physiother Theory Pract. 2021 Jan;37(1):81-88.

Background: To evaluate the functional capacity in children and adolescents with cystic fibrosis (CF) through the pediatric Glittre ADL-test (TGlittre-P) and its implications for respiratory mechanics, physiological parameters and clinical markers. 

Methods: Impulse oscillometry system (IOS) parameters, vital signs (heart rate, respiratory rate and blood pressure), perception of dyspnea and peripheral oxygen saturation (SpO2) were assessed before and immediately after the TGlittre-P. Test performance was correlated with age, quality of life, disease severity, nutrition, spirometry and IOS parameters. 

Results: Twenty-six patients were included thirteen boys, mean age of 9.54 ± 1.94 and FEV1 of 71.45%±22.67%. The mean time to complete the test was 2.94 min, similar to that predicted for healthy children. There was a correlation of time with age, as well as with some IOS parameters. Disease severity, spirometric parameters, nutritional aspects and quality of life (QoL) were correlated with performance in the TGlittre-P. Immediate increase of vital signs and decline in SpO2 were observed after the test, without an impact on IOS parameters. 

Conclusion: Patients with CF showed similar performance and changes of vital signs at the TGlittre-P compared to reference values for healthy children. There were no immediate changes in parameters for the assessed respiratory mechanics. Also, there was no correlation of time to complete the TGLittre-P test with respiratory mechanics, physiological parameters and clinical markers.

 

Identifying pediatric lung disease: A comparison of forced oscillation technique outcomes. Evans DJ, Schultz A, Verheggen M, Hall GL, Simpson SJ.Pediatr Pulmonol. 2019 Jun;54(6):751-758.

Rationale: Increasing evidence suggests the forced oscillation technique (FOT) has the capacity to provide non-invasive monitoring and diagnosis of respiratory disease in young children. However, which FOT outcomes provide the most pertinent clinical information is currently unknown. The aim of this study was to determine which FOT outcomes were most sensitive for differentiating between health and specific childhood respiratory disease.

Methods: Respiratory impedance was measured using a commercial device (i2M, Chess Medical, Belgium) in children aged between 3 and 7 years, who had been diagnosed with either cystic fibrosis (N = 84), asthma (N = 99) or were born very preterm (N = 114). Z-scores were calculated for respiratory system resistance (Rrs) and reactance (Xrs) at 6, 8, and 10 Hz, the resonance frequency (Fres), frequency dependence (Fdep4-24 ), and area under the reactance curve (AX). Pairwise comparisons of the area under the receiver operating characteristic (ROC) curve were used to determine the most relevant FOT variables.

Results and conclusions: The FOT outcomes best able to discern between health and disease were Fres (P < 0.0001) in cystic fibrosis, Fres (P < 0.0001) in asthma and Xrs8 (P < 0.0001) in children born preterm. These findings suggest the utility of specific FOT outcomes is dependent on the respiratory disease being assessed. It is hoped that a disease-specific approach to interpreting FOT data can help further refine the FOT technique to aid in the diagnosis of children with pediatric respiratory disease.

 

Within-breath changes in respiratory system impedance in children with cystic fibrosis. Zannin E, Nyilas S, Ramsey KA, Latzin P, Dellaca' RL. Pediatr Pulmonol. 2019 Jun;54(6):737-742.

Background: The aim of this study was to assess within-breath respiratory system impedance by the forced oscillation technique (FOT) in children with cystic fibrosis (CF) and relate it to the underlying lung disease.

Methods: Thirty-three children with CF (median [range] age 12.0 [6-17] years) underwent FOT at 8 Hz during tidal breathing, multiple breath nitrogen washout (LCI), spirometry (FEV1), body plethysmography (RV/TLC), and magnetic resonance imaging (MRI). FOT outcomes included: mean inspiratory, expiratory, and whole breath resistance (R8INSP , R8EXP , R8TOT ) and reactance (X8INSP , X8EXP , X8TOT ), and the differences between X8INSP and X8EXP (ΔX8). Morphological changes were evaluated by MRI using CF-specific morphological scores. Spearman correlation was performed to examine the correlation between FOT indices and other parameters.

Results: FEV1 was negatively correlated with R8EXP (r = -0.52, P = 0.002) and ΔX8 (r = -0.55, P = 0.001), and positively correlated with and X8EXP (r = 0.56, P < 0.001). RV/TLC was positively correlated with R8EXP (r = 0.43, P = 0.013), and ΔX8 (r = 0.54, P = 0.001) and negatively correlated with X8EXP (r = -0.54, P = 0.001). We found poor correlation between FOT parameters and LCI and no correlation between FOT parameters and MRI scores.

Conclusion: In children with CF, changes in within-breath FOT parameters are consistent with peripheral obstruction and dynamic airway compression, while they are not associated with ventilation heterogeneities and morphological alterations.