
==== Front
Ital J Pediatr
Ital J Pediatr
Italian Journal of Pediatrics
1824-7288
BioMed Central London

39232791
1716
10.1186/s13052-024-01716-8
Research
The role of respiratory function tests in infants with stridor: diagnosis at glance and follow-up
http://orcid.org/0000-0002-2853-8318
Bloise Silvia silvia.bloise1989@gmail.com

Nenna Raffaella
Petrarca Laura
Conti Maria Giulia
Di Mattia Greta
Matera Luigi
Mancino Enrica
La Regina Domenico Paolo
Lubrano Riccardo
Bonci Enea
Moretti Corrado
Midulla Fabio
https://ror.org/02be6w209 grid.7841.a Dipartimento Materno Infantile e di Scienze Urologiche, Sapienza Università di Roma, UOC di Pediatria e Neonatologia Ospedale Santa Maria Goretti, Polo Pontino, Roma, Italy
4 9 2024
4 9 2024
2024
50 1644 2 2024
28 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Background

Recently, the development of advanced, noninvasive methods has allowed the study of respiratory function even in uncooperative infants. To date, there is still little data on the application of this technique in infants with suspected airway obstruction. The aims of our study were:

- To evaluate the role of respiratory function testing (PFR) in the diagnosis and follow-up of infants with stridor

- To evaluate the differences between patients with inspiratory stridor and expiratory stridor.

- To evaluate the concordance between PFR and endoscopy.

Methods

We enrolled infants aged < 1 year with a diagnosis of inspiratory and/or expiratory chronic stridor and a group of healthy controls. For each patient we performed PFR at diagnosis (T0) and for cases at follow-up, at 3 months (T1), 6 months (T2), 12 months (T3). At T0, all patients were classified according to a clinical score, and at follow-up, stature-ponderal growth was assessed.

When clinically indicated, patients underwent bronchoscopy.

Results

We enrolled 48 cases (42 diagnosed with inspiratory stridor and 6 expiratory stridor) and 26 healthy controls. At T0, patients with stridor had increased inspiratory time (p < 0.0001) and expiratory time (p < 0.001) than healthy controls and abnormal curve morphology depending on the type of stridor. At T0, patients with expiratory stridor had a reduced Peak expiratory flow (p < 0.023) and a longer expiratory time (p < 0.004) than patients with inspiratory stridor.

We showed an excellent concordance between PFR and endoscopic examination (k = 0.885, p < 0.0001). At follow-up, we showed a progressive increase of the respiratory parameters in line with the growth.

Conclusions

PFR could help improve the management of these patients through rapid and noninvasive diagnosis, careful monitoring, and early detection of those most at risk.

Keywords

Respiratory function testing
Stridor
Infant
Airway obstruction
issue-copyright-statement© Società Italiana di Pediatria 2024
==== Body
pmcBackground

Stridor is a high-frequency musical sound generated by the vibration of obstructed airways as a result of turbulent airflow. Depending on the site of the obstruction, the stridor may be inspiratory, if extrathoracic airway (nose, pharynx, larynx, and trachea) are involved, or expiratory, if the obstruction is located in the intrathoracic airway (tracheobronchial tree) [1, 2].

Stridor can be congenital or acquired. The acquired stridor is generally acute, mainly manifest at after 6 months of age and can be caused by infection, foreign body aspiration and iatrogenic insults; while congenital stridor has a chronic course and tends to occur at birth or in the first few months of life [3]. Laryngomalacia represents the most frequent congenital cause of stridor in the first year of life, 90% of patients are managed conservatively with resolution of symptoms by 12–24 months of age [4–6].

Other causes of stridor can be vocal cord paresis, laryngeal webs, congenital subglottic stenosis, tracheomalacia, tracheal stenosis and subglottic hemangioma [7–11].

To date, the gold standard for the diagnosis in patients with suspected airway obstruction is the airway endoscopic, that is generally reserved only in moderate e sever cases [12–14].

However, it appears evident how the stridor can be caused by a variety of conditions from benign, self-limited diseases to life-threatening requiring rapid intervention.

Therefore, it is necessary to identify a first-level, noninvasive tool in the management of infants with stridor in order to guide the clinician in the diagnostic-therapeutic pathway.

Recently, advances in technology have allowed the development of no invasive techniques to study respiratory function, also in uncooperative infants. In particular, tidal breathing flow-volume loop (TB-FV) and the multiple breath washout (MBW) are becoming increasingly helpful in pediatric practice in a large variety of respiratory conditions [15–18]. However, there are still few data on their application in infants with suspected airway obstruction.

In this context, we wanted to conduct a study to evaluate the role of respiratory function testing in a cohort of infants with stridor. The aims of our study were: 1) to evaluate the role of respiratory function testing (PFR) in the diagnosis and follow-up of infants with stridor; 2) to evaluate the differences between patients with inspiratory stridor and expiratory stridor; 3) to evaluate the concordance between PFR and endoscopy.

Methods

Study design

This was a retrospective study conducted in the Department of Pediatrics of the University “La Sapienza” of Rome from October 2021 to September 2023.

Participants

We enrolled infants full-term younger than 12 months with a clinical diagnosis of chronic inspiratory e/o expiratory stridor (cases) and a group of patients with negative past history for respiratory diseases (controls).

Chronic stridor is a stridor that is present at birth or shortly thereafter, not acutely. It is daily, increases during crying and not related to infection, to foreign body aspiration and iatrogenic insults.

Exclusion criteria were: age > 12 months, prematurity, patients with previous endoscopic evaluations, other comorbidities (chronic respiratory disease, cardiac diseases, genetic diseases, neuromuscular diseases).

Procedures

Demographic characteristics and medical history including age, height, weight, breastfeeding, type of birth, family history of atopy, exposure to smoke were obtained during the first visit.

Patient cases were classified into three groups according to a clinical score [19]: mild (isolated stridor); moderate (stridor associated with cough, regurgitation or difficulty feeding); severe (stridor associated with apnea, cyanosis, growth failure).

After a first pediatric assessment, all subjects underwent a TB–FV loop study (T0); Based on morphological findings at TB-FV, we identified 4 specific patterns: pattern 1 characterized by deep fluctuations of inspiratory flow rate with normal expiratory phase (suspected extrathoracic obstruction), pattern 2 characterized by expiratory flattening with normal inspiratory phase (suspected intrathoracic obstruction), pattern 3 with involvement of both respiratory phases (suspected intra and extrathoracic obstruction) and pattern 4 with round or oval conformation ( healthy patients).

When clinically indicated, specifically patients with moderate and severe forms of stridor underwent bronchoscopy.

Patient cases underwent TB–FV loop study at follow-up, respectively 3 months (T1), 6 months (T2) and 12 months (T3) from T0.

Tidal breathing flow-volume loop

The TB-FV loops were recorded with a computerized infant pulmonary function device (“Exhalyzer and Spiroware”, ECO MEDICS, Bubikonerstr. 45, CH-8635 Duernten Switzerland), allowing immediate graphic visualization of flow-volume curve. The airway functional study was performed during quiet sleep, in a supine position with the head midline and the neck slightly extended to minimize airway or glottis obstruction. A face mask of size 1 or 2 was utilized according to the size and weight of each patient, in adherence with the American Thoracic Society/European.

Respiratory Society recommendations and positioned in such a way to cover the mouth and the nose, not allowing air leak [20, 21]. The machine was calibrated according to the infant’s weight and length at each test. At least three consecutive breaths were set as minimum required to have a valid test.

The main parameters of the TB-FV loop registered were tidal volume (VT), tidal volume per kg (VT/kg), inspiratory and expiratory volumes (VI and VE), inspiratory and expiratory times (Ti and Te), time-to-peak tidal expiratory flow as a percentage of total expiratory time (TPTEF/Te), peak inspiratory and expiratory flows (PIF, PEF), respiratory rate (RR) [22].

Bronchoscopy

Subjects were sedated with midazolam, fentanest and propofol intravenously. During the procedure hearth rate, respiratory rate, and pulse oximetry were recorded. Bronchoscopy was performed via the nasal route, using pediatric flexible bronchoscope (Pentax). Airway findings were videotaped.

Statistical analysis

Statistical analysis was performed using SPSS statistical software (version 27, IBM, New York, USA). A descriptive analysis was performed for all the variables studied using percentage values ​​for the qualitative variables, and the mean values ​​and relative standard deviations for the quantitative variables. For the discrete variables, non-parametric univariate statistics tests were used (X2 test and Fischer’s exact test for very low frequencies). The Spearman coefficient test was used to study the correlation between quantitative variables. For concordance analysis, we used the Test Kappa of Cohen. P values < 0.05 were considered significant.

Results

Demographics and clinical characteristics

We enrolled 74 patients; 48 infants with a clinical diagnosis of chronic stridor, respectively 42 with inspiratory stridor and six with expiratory stridor (group of cases) and 26 healthy infants (group of controls). For cases, the mean age was 2.45 (± 2.12 months); for controls 2.76 (± 4.24) months.

Cases were subdivided in 3 groups, according to clinical score: mild (composed by 32 patients), moderate (12 patients), severe (4 patients).

Demographics and Clinical Characteristics are summarized in Table 1.Table 1 Demographics and clinical characteristics of patients enrolled

	Cases	Controls	P < 0.05	
Cases/Controls, n	48	26		
Gender, M (%)	32 (66.7)	16 (61.5)	0.66	
Age, Months (SD)	2.48 ± (1.62)	2.47 ± (2.26)	0.98	
Weight, Kg (SD)	5.12 ± (1.48)	4.90 ± (1.95)		
Lenght, cm (SD)	56.85 ± (8.87)	57.98 ± (5.39)		
Breastfeeding (%)	55.6			
Family atopy (%)	57.1			
Smoke (%)	25.4			
Clinical score, n(%)	Mild: 32 (66.7)

Moderate: 12 (25.0)

Severe: 4 (8.3)

			

Tidal breathing flow-volume loop at first evaluation (T0)

Comparison of cases and controls

At first evaluation (T0), cases showed 3 different morphological patterns: pattern 1 characterized by deep fluctuations of inspiratory flow rate with normal expiratory phase (41 patients with inspiratory stridor); pattern 2 characterized by expiratory flattening with normal inspiratory phase (4 patients with expiratory stridor); pattern 3 with involvement of both respiratory phases (3 patients with bifasic stridor inspiratory and expiratory). While controls showed a round or oval conformation (Fig. 1).Fig. 1 Different morphological patterns of the TV-FV loop: pattern 1: patients with inspiratory stridor; pattern 2: patients with expiratory stridor; healthy control

Respiratory parameters obtained by recording TB–FV in the 2 group of patients are reported in Table 2. Patient cases had significantly longer inspiratory and expiratory than controls (Ti: p < 0.0001; Te: p < 0.001).Table 2 Respirator parameters of TB-FV at first evaluation (T): comparison cases and controls

	VINS	VESP	VT/Kg	PIF	PEF	TI	TE	TPTEF/TE	
Cases	43.00 ± 15.56	40.45 ± 13.94	8.20 ± 2.38	112.82 ± 50.59	100.50 ± 52.90	0.58 ± 0.17	0.66 ± 0.25	32.15 ± 12.84	
Controls	38.40 ± 16.43	37.57 ± 16.79	7.97 ± 2.22	114.70 ± 48.25	108.77 ± 46.25	0.44 ± 0.07	0.49 ± 0.10	36.67 ± 9.54	
P value	0.94	0.32	0.65	0.74	0.07	0.0001	0.001	0.048	

Comparison patients with inspiratory stridor and expiratory stridor

Comparing respiratory parameters of patients with different type of stridor, we observed that patients with expiratory stridor had a lower peak expiratory flow and increased expiratory time than patients with inspiratory stridor (PEF: p < 0.023; Te: p < 0.004) (Fig. 2).Fig. 2 Differences of respiratory parameter between patients with inspiratory stridor and patients with expiratory stridor

Furthermore, we observed that a reduced peak expiratory flow and increased expiratory time were associated with more severe clinical forms of stridor (PEF: p < 0.008; Te: p < 0.04).

Concordance between TB-FV loop and bronchoscopy

In our case group, 16 patients in the moderate and severe group underwent endoscopic examination.

The endoscopic diagnosis were: laryngomalacia (9 cases), subglottic hemangioma (1 case), tracheal stenosis (1 case), tracheomalacia (2 case), concomitant laryngomalacia and tracheomalacia (2 cases), suis bronchus (1 case).

We demonstrated an excellent concordance between the diagnostic suspicion at the curve (intrathoracic obstruction, extrathoracic obstruction, or both) and endoscopic diagnosis (k = 0.885, p < 0.0001). Figure 3 shows the most relevant endoscopic findings.Fig. 3 This figure includes the most the most relevant endoscopic findings: upper left shows laryngomalacia, upper right a subglottic hemangioma, below a tracheal stenosis

Tidal breathing flow-volume loop at follow-up

The follow-up was conducted after 3 months (T1), 6 months (T2), 12 months (T3) from T0.

We performed TB-FV in 30 patients at T1; in 24 patients at T2; in 14 patients at T3.

Table 3 report respiratory parameters of TB–FV loop at the three follow-ups. We showed a progressive increase in all respiratory parameters and a reduction of respiratory rate in accordance with staturo-ponderal growth and clinical improvement (Fig. 4).Table 3 Respirator parameters of TB-FV at follow-up

	VINS	V ESP	RR	VT	PIF	PEF	TI	TE	TPTEF/TE	
T0	43.0 ± 15.6	40.5 ± 13.9	50.1 ± 12.1	42.4 ± 14.4	112.8 ± 50.6	100.5 ± 32.9	0.6 ± 0.2	0.7 ± 0.3	32.2 ± 12.8	
T1	58.6 ± 15.6	57.0 ± 14	42.5 ± 11.1	57.2 ± 15.2	123.9 ± 35.4	112.3 ± 29.3	0.7 ± 0.1	0.8 ± 0.2	27.2 ± 10.5	
T2	77.9 ± 27.5	75.2 ± 20.5	36.2 ± 11.4	76.6 ± 23.7	147.6 ± 77.4	119.8 ± 37.3	0.8 ± 0.2	1.1 ± 0.7	29.0 ± 15.1	
T3	102.6 ± 28.4	100.1 ± 28.3	31.3 ± 8.4	101.4 ± 28.1	159.2 ± 29.2	136.2 ± 31.5	0.9 ± 0.2	1.2 ± 0.3	27.1 ± 10.3	

Fig. 4 Increase of respiratory parameters (inspiratory and expiratory volume, peak inspiratory and expiratory flow) at follow-up

Discussion

In recent years, there was growing evidence for the use of lung function testing in infancy in various respiratory diseases [23–28], but to date many clinicians still consider these methods as experimental and limited to the scope of the research.

Our findings supported the usefulness in the management of infants with suspected airway obstruction. At first evaluation, primary information derived by the graphic representation of the TB–FV. We showed different patterns depending of the site of obstruction: pattern 1 characterized by fluttering of the inspiratory phase, pattern 2 characterized by expiratory flattening, pattern 3 characterized by both components. These patterns are easily recognizable when compared with healthy infants who have a round or oval shape. In this way, only at a glance can suspicion be placed on the type of airway obstruction [29–31].

Comparing respiratory parameters recorded between case patients and controls, we showed that case patients have longer inspiratory and expiratory times than controls. These findings are consistent with the presence of airway obstruction impeding airflow, however they have low diagnostic utility because there is a large intra-subject and intersubject variability [31, 32].

Instead, interesting results derived by comparison between patients with different type of stridor; in fact, patients with expiratory stridor present a reduced expiratory peak flow and a longer expiratory time than patients with inspiratory stridor. These data in association with graphic representation of the loop add to the clinician information on the type of respiratory obstruction.

Secondary we demonstrated excellent diagnostic concordance between respiratory function tests and endoscopy. These data are in line with other studies of literature [33] and represents those could have the most important implications in clinical practice. In our study patients with pattern 1 had as endoscopic diagnosis laryngomalacia, patients with pattern 2 had as endoscopic diagnosis conditions such as: tracheomalacia, tracheal stenosis, subglottic hemangioma, patients with pattern 3 had involvement of both the larynx and the intrathoracic trachea.

In this context, Tidal breathing flow-volume loop could be a valid screening tool able to discriminate patients with isolated laryngomalacia who do not need endoscopic examination, thus reducing invasive procedures and costs; Certainly, in association with clinical evaluation and physical examination.

An innovative aspect of our study is the evaluation of respiratory parameters of the curve correlated with clinical severity. In fact, to date no significant differences in respiratory curve parameters have been described between patients with different degrees of obstruction [34]. We found that lower peak expiratory flow and longer expiratory time were associated with severe forms of stridor. This aspect is important in identifying the most at-risk patients and initiating early second-level diagnostic investigations such as endoscopy and targeted therapeutic strategies.

Finally, we performed the TB-FV at 3, 6, and 12 months of first evaluation. Few are the study present in literature that evaluated the application of the methodic at follow-up. We showed a progressive increase in all respiratory parameters and a reduction in respiratory rate in accordance with staturo-ponderal growth and clinical improvement. This approach could be helpful both in patients managed conservatively to add information to clinical examination and to reassure caregivers about the benignity and resolution of the condition, both in those undergoing surgery [35] to verify the improvement in breathing patterns and monitor future respiratory development in these infants.

Despite the many advantages of this method, it is important to underline that this new diagnostic tool presents some limitation: it can be influenced by many factors as light sleep, the timing of the last meal (because the full stomach can alter the test), the size of the mask.

Therefore, it is important to perform the test when patients are sleeping soundly, away from the last meal, and with a correctly sized mask to reduce potential bias.

This study has some limitation: the small number of patients enrolled; not all patients performed bronchoscopy and the lack of complete follow-up for all patients.

Conclusion

Our findings confirm the validity of the use of TB-FV loop analysis in the management of infants with suspected airway obstruction. The advantages of the method (simplicity, rapidity, non-invasiveness) make it an excellent screening tool in the hands of the clinician to reduce the use of invasive procedures in mild self-limiting cases and to select the most at-risk patients early. This approach could contribute to a better use of economic resources of the health system and to improve the quality of pediatric care.

Abbreviations

PFR Respiratory function tests

TB-FV Tidal breathing flow-volume

Acknowledgements

Not applicable.

Authors’ contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SB, RN, LP, MC, EM, GD, DPR, LM, EB, RL. The first draft of the manuscript was written by SB, RN, LP and all authors commented on previous versions of the manuscript. Prof. FM, Prof RN, Prof CM conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

None.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

A verbal informed consent was obtained by each participant before the study. The study was exempt from ethical approval.

All methods were performed in accordance with the ethical standards as laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Zalzal HG Zalzal GH Stridor in the infant patient Pediatr Clin North Am 2022 69 2 301 317 10.1016/j.pcl.2021.12.003 35337541
Zalzal HG, Zalzal GH. Stridor in the infant patient. Pediatr Clin North Am. 2022;69(2):301–17. 10.1016/j.pcl.2021.12.003.35337541 10.1016/j.pcl.2021.12.003
2. Bluher AE Darrow DH Stridor in the newborn Pediatr Clin North Am 2019 66 2 475 488 10.1016/j.pcl.2018.12.013 30819349
Bluher AE, Darrow DH. Stridor in the newborn. Pediatr Clin North Am. 2019;66(2):475–88. 10.1016/j.pcl.2018.12.013.30819349 10.1016/j.pcl.2018.12.013
3. Boudewyns A Claes J Van de Heyning P Clinical practice: an approach to stridor in infants and children Eur J Pediatr 2010 169 2 135 141 10.1007/s00431-009-1044-7 19763619
Boudewyns A, Claes J, Van de Heyning P. Clinical practice: an approach to stridor in infants and children. Eur J Pediatr. 2010;169(2):135–41. 10.1007/s00431-009-1044-7.19763619 10.1007/s00431-009-1044-7
4. Bedwell J Zalzal G Laryngomalacia Semin Pediatr Surg 2016 25 3 119 122 10.1053/j.sempedsurg.2016.02.004 27301595
Bedwell J, Zalzal G. Laryngomalacia. Semin Pediatr Surg. 2016;25(3):119–22. 10.1053/j.sempedsurg.2016.02.004.27301595 10.1053/j.sempedsurg.2016.02.004
5. Thorne MC Garetz SL Laryngomalacia: review and summary of current clinical practice in 2015 Paediatr Respir Rev 2016 17 3 8 10.1016/j.prrv.2015.02.002 25802018
Thorne MC, Garetz SL. Laryngomalacia: review and summary of current clinical practice in 2015. Paediatr Respir Rev. 2016;17:3–8. 10.1016/j.prrv.2015.02.002.25802018 10.1016/j.prrv.2015.02.002
6. Midulla F Guidi R Tancredi G Quattrucci S Ratjen F Bottero S Microaspiration in infants with laryngomalacia Laryngoscope 2004 114 9 1592 1596 10.1097/00005537-200409000-00017 15475788
Midulla F, Guidi R, Tancredi G, Quattrucci S, Ratjen F, Bottero S, et al. Microaspiration in infants with laryngomalacia. Laryngoscope. 2004;114(9):1592–6. 10.1097/00005537-200409000-00017.15475788 10.1097/00005537-200409000-00017
7. Clark CM Kugler K Carr MM Common causes of congenital stridor in infants JAAPA 2018 31 11 36 40 10.1097/01.JAA.0000546480.64441.af 30358678
Clark CM, Kugler K, Carr MM. Common causes of congenital stridor in infants. JAAPA. 2018;31(11):36–40. 10.1097/01.JAA.0000546480.64441.af.30358678 10.1097/01.JAA.0000546480.64441.af
8. Pfleger A Eber E Assessment and causes of stridor Paediatr Respir Rev 2016 18 64 72 10.1016/j.prrv.2015.10.003 26707546
Pfleger A, Eber E. Assessment and causes of stridor. Paediatr Respir Rev. 2016;18:64–72. 10.1016/j.prrv.2015.10.003.26707546 10.1016/j.prrv.2015.10.003
9. Robitaille C Fortin M Trahan S Delage A Simon M Subglottic hemangioma J Bronchology Interv Pulmonol 2016 23 3 232 235 10.1097/LBR.0000000000000282 27261932
Robitaille C, Fortin M, Trahan S, Delage A, Simon M. Subglottic hemangioma. J Bronchology Interv Pulmonol. 2016;23(3):232–5. 10.1097/LBR.0000000000000282.27261932 10.1097/LBR.0000000000000282
10. Kumar P Goyal JP Clinical characteristics of tracheomalacia in infants Indian Pediatr 2019 56 3 253 254 30955006
Kumar P, Goyal JP. Clinical characteristics of tracheomalacia in infants. Indian Pediatr. 2019;56(3):253–4.30955006
11. Sengupta A Murthy RA Congenital tracheal stenosis & associated cardiac anomalies: operative management & techniques J Thorac Dis 2020 12 3 1184 1193 10.21037/jtd.2019.10.42 32274199
Sengupta A, Murthy RA. Congenital tracheal stenosis & associated cardiac anomalies: operative management & techniques. J Thorac Dis. 2020;12(3):1184–93. 10.21037/jtd.2019.10.42.32274199 10.21037/jtd.2019.10.42
12. Holinger LD Etiology of stridor in the neonate, infant and child Ann Otol Rhinol Laryngol 1980 89 397 400 10.1177/000348948008900502 7436240
Holinger LD. Etiology of stridor in the neonate, infant and child. Ann Otol Rhinol Laryngol. 1980;89:397–400.7436240 10.1177/000348948008900502
13. Tostevin PMJ deBruin R Hosni A Evans JNG The value of radiological investigations in pre-endoscopic assessment of children with stridor J Laryngol Otol 1995 109 844 848 10.1017/S0022215100131470 7494117
Tostevin PMJ, deBruin R, Hosni A, Evans JNG. The value of radiological investigations in pre-endoscopic assessment of children with stridor. J Laryngol Otol. 1995;109:844–8.7494117 10.1017/S0022215100131470
14. Plácido-Paias R Delgado-Pecellín I González-Valencia JP Fiberoptic bronchoscopy findings in children with stridor in a tertiary hospital Arch Bronconeumol 2016 52 6 335 336 10.1016/j.arbres.2015.09.007 26548504
Plácido-Paias R, Delgado-Pecellín I, González-Valencia JP. Fiberoptic bronchoscopy findings in children with stridor in a tertiary hospital. Arch Bronconeumol. 2016;52(6):335–6. 10.1016/j.arbres.2015.09.007.26548504 10.1016/j.arbres.2015.09.007
15. Beydon N Davis SD Lombardi E Allen JL Arets HG Aurora P An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children Am J Respir Crit Care Med 2007 175 12 1304 1345 10.1164/rccm.200605-642ST 17545458
Beydon N, Davis SD, Lombardi E, Allen JL, Arets HG, Aurora P, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007;175(12):1304–45. 10.1164/rccm.200605-642ST.17545458 10.1164/rccm.200605-642ST
16. Rusconi F Lombardi E Spada E Brescianini S Culasso M Di Toro F Lung function at school age in infants with lower respiratory tract infections with and without wheezing: a birth cohort study Pediatr Pulmonol 2022 57 4 857 861 10.1002/ppul.25835 35048563
Rusconi F, Lombardi E, Spada E, Brescianini S, Culasso M, Di Toro F, et al. Lung function at school age in infants with lower respiratory tract infections with and without wheezing: a birth cohort study. Pediatr Pulmonol. 2022;57(4):857–61. 10.1002/ppul.25835.35048563 10.1002/ppul.25835
17. Leonhardt S Ahrens P Kecman V Analysis of tidal breathing flow volume loops for automated lung-function diagnosis in infants IEEE Trans Biomed Eng 2010 57 8 1945 1953 10.1109/TBME.2010.2046168 20483693
Leonhardt S, Ahrens P, Kecman V. Analysis of tidal breathing flow volume loops for automated lung-function diagnosis in infants. IEEE Trans Biomed Eng. 2010;57(8):1945–53. 10.1109/TBME.2010.2046168.20483693 10.1109/TBME.2010.2046168
18. Davies G Aurora P The use of multiple breath washout for assessing cystic fibrosis in infants Expert Rev Respir Med 2017 11 1 21 28 10.1080/17476348.2017.1269604 27927050
Davies G, Aurora P. The use of multiple breath washout for assessing cystic fibrosis in infants. Expert Rev Respir Med. 2017;11(1):21–8. 10.1080/17476348.2017.1269604.27927050 10.1080/17476348.2017.1269604
19. Carter J Rahbar R Brigger M Chan K Cheng A Daniel SJ International Pediatric ORL Group (IPOG) laryngomalacia consensus recommendations Int J Pediatr Otorhinolaryngol 2016 86 256 261 10.1016/j.ijporl.2016.04.007 27107728
Carter J, Rahbar R, Brigger M, Chan K, Cheng A, Daniel SJ, et al. International Pediatric ORL Group (IPOG) laryngomalacia consensus recommendations. Int J Pediatr Otorhinolaryngol. 2016;86:256–61. 10.1016/j.ijporl.2016.04.007.27107728 10.1016/j.ijporl.2016.04.007
20. Frey U Stocks J Sly P Bates J Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society Eur Respir J 2000 16 1016 22 10.1183/09031936.00.16510160 11153570
Frey U, Stocks J, Sly P, Bates J. Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur Respir J. 2000;16:1016–22.11153570 10.1183/09031936.00.16510160
21. Frey U Stocks J Coates A Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society Eur Respir J 2000 16 731 40 10.1034/j.1399-3003.2000.16d28.x 11106221
Frey U, Stocks J, Coates A, et al. Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur Respir J. 2000;16:731–40.11106221 10.1034/j.1399-3003.2000.16d28.x
22. Fuchs O Latzin P Thamrin C Stern G Frischknecht P Singer F Normative data for lung function and exhaled nitric oxide in unsedated healthy infants Eur Respir J 2011 37 5 1208 1216 10.1183/09031936.00125510 21109556
Fuchs O, Latzin P, Thamrin C, Stern G, Frischknecht P, Singer F, et al. Normative data for lung function and exhaled nitric oxide in unsedated healthy infants. Eur Respir J. 2011;37(5):1208–16. 10.1183/09031936.00125510.21109556 10.1183/09031936.00125510
23. Robinson PD Latzin P Verbanck S Hall GL Horsley A Gappa M Consensus statement for inert gas washout measurement using multiple and single breath tests Eur Respir J 2013 41 507 522 10.1183/09031936.00069712 23397305
Robinson PD, Latzin P, Verbanck S, Hall GL, Horsley A, Gappa M, et al. Consensus statement for inert gas washout measurement using multiple and single breath tests. Eur Respir J. 2013;41:507–22.23397305 10.1183/09031936.00069712
24. Lavizzari A Zannin E Ophorst M Ciuffini F Gangi S Farolfi A Tidal breathing measurements in former preterm infants: a retrospective longitudinal study J Pediatr 2021 230 112 118.e4 10.1016/j.jpeds.2020.11.050 33253731
Lavizzari A, Zannin E, Ophorst M, Ciuffini F, Gangi S, Farolfi A, et al. Tidal breathing measurements in former preterm infants: a retrospective longitudinal study. J Pediatr. 2021;230:112-118.e4. 10.1016/j.jpeds.2020.11.050.33253731 10.1016/j.jpeds.2020.11.050
25. Han W Xie Y Ren SY Yin LM Fen XY Deng XH Clinical application of tidal breathing lung function test in 1–4 years old children with wheezing diseases Zhongguo Dang Dai Er Ke Za Zhi 2014 16 8 800 804 25140771
Han W, Xie Y, Ren SY, Yin LM, Fen XY, Deng XH, et al. Clinical application of tidal breathing lung function test in 1–4 years old children with wheezing diseases. Zhongguo Dang Dai Er Ke Za Zhi. 2014;16(8):800–4.25140771
26. Ring AM Carlens J Bush A Castillo-Corullón S Fasola S Gaboli MP Pulmonary function testing in children's interstitial lung disease Eur Respir Rev 2020 29 157 200019 10.1183/16000617.0019-2020 32699025
Ring AM, Carlens J, Bush A, Castillo-Corullón S, Fasola S, Gaboli MP, et al. Pulmonary function testing in children’s interstitial lung disease. Eur Respir Rev. 2020;29(157):200019. 10.1183/16000617.0019-202032699025 10.1183/16000617.0019-2020
27. Fainardi V Lombardi E Lung function tests to monitor respiratory disease in preschool children Acta Biomed 2018 89 2 148 156 10.23750/abm.v89i2.7155 29957746
Fainardi V, Lombardi E. Lung function tests to monitor respiratory disease in preschool children. Acta Biomed. 2018;89(2):148–56. 10.23750/abm.v89i2.7155.29957746 10.23750/abm.v89i2.7155
28. Nyilas S Schlegtendal A Singer F Goutaki M Kuehni CE Casaulta C Alternative inert gas washout outcomes in patients with primary ciliary dyskinesia Eur Respir J 2017 49 1 1600466 10.1183/13993003.00466-2016 28122863
Nyilas S, Schlegtendal A, Singer F, Goutaki M, Kuehni CE, Casaulta C, et al. Alternative inert gas washout outcomes in patients with primary ciliary dyskinesia. Eur Respir J. 2017;49(1):1600466. 10.1183/13993003.00466-2016.28122863 10.1183/13993003.00466-2016
29. Saunders C Bayfield K Irving S Short C Bush A Davies JC Developments in multiple breath washout testing in children with cystic fibrosis Curr Med Res Opin 2017 33 4 613 620 10.1080/03007995.2016.1268999 27931123
Saunders C, Bayfield K, Irving S, Short C, Bush A, Davies JC. Developments in multiple breath washout testing in children with cystic fibrosis. Curr Med Res Opin. 2017;33(4):613–20. 10.1080/03007995.2016.1268999.27931123 10.1080/03007995.2016.1268999
30. Abramson A Goldstein M Stenzler A Steele A The use of the tidal breathing flow-volume loop in laryngotracheal disease of neonates and infants Laryngoscope 1982 91 922 926 10.1288/00005537-198208000-00013
Abramson A, Goldstein M, Stenzler A, Steele A. The use of the tidal breathing flow-volume loop in laryngotracheal disease of neonates and infants. Laryngoscope. 1982;91:922–6.10.1288/00005537-198208000-00013
31. Lodrup Carlsen KC Tidal breathing analysis in infants and preschool children: tidal flow volume loops. In: Zach M, Carlsen KH, Warner JO, Sennhauser FH, editors. New diagnostic techniques in paediatric respiratory medicine Eur Respir Monogr 1997 5 27 57
Lodrup Carlsen KC. Tidal breathing analysis in infants and preschool children: tidal flow volume loops. In: Zach M, Carlsen KH, Warner JO, Sennhauser FH, editors. New diagnostic techniques in paediatric respiratory medicine. Eur Respir Monogr. 1997;5:27–57.
32. Filippone M Narne S Pettenazzo A Zacchello F Baraldi E Functional approach to infants and young children with noisy breathing: validation of pneumotachography by blinded comparison with bronchoscopy Am J Respir Crit Care Med 2000 162 5 1795 1800 10.1164/ajrccm.162.5.9912008 11069815
Filippone M, Narne S, Pettenazzo A, Zacchello F, Baraldi E. Functional approach to infants and young children with noisy breathing: validation of pneumotachography by blinded comparison with bronchoscopy. Am J Respir Crit Care Med. 2000;162(5):1795–800. 10.1164/ajrccm.162.5.9912008.11069815 10.1164/ajrccm.162.5.9912008
33. Seppä VP Hult A Gracia-Tabuenca J Paassilta M Viik J Plavec D Airway obstruction is associated with reduced variability in specific parts of the tidal breathing flow-volume curve in young children ERJ Open Res 2019 5 2 00028 2019 10.1183/23120541.00028-2019 31218218
Seppä VP, Hult A, Gracia-Tabuenca J, Paassilta M, Viik J, Plavec D, et al. Airway obstruction is associated with reduced variability in specific parts of the tidal breathing flow-volume curve in young children. ERJ Open Res. 2019;5(2):00028–2019. 10.1183/23120541.00028-2019.31218218 10.1183/23120541.00028-2019
34. Columbo C Landolfo F De Rose DU Massolo AC Secinaro A Santangelo TP The role of lung function testing in newborn infants with congenital thoracic arterial anomalies Front Pediatr 2021 9 682551 10.3389/fped.2021.682551 34211945
Columbo C, Landolfo F, De Rose DU, Massolo AC, Secinaro A, Santangelo TP, et al. The role of lung function testing in newborn infants with congenital thoracic arterial anomalies. Front Pediatr. 2021;9:682551. 10.3389/fped.2021.682551.34211945 10.3389/fped.2021.682551
35. Cialente F Meucci D Tropiano ML Salvati A Torsello M Savignoni F Changes in breathing patterns after surgery in severe laryngomalacia Children (Basel) 2021 8 12 1120 10.3390/children8121120 34943316
Cialente F, Meucci D, Tropiano ML, Salvati A, Torsello M, Savignoni F, et al. Changes in breathing patterns after surgery in severe laryngomalacia. Children (Basel). 2021;8(12):1120. 10.3390/children8121120.34943316 10.3390/children8121120
