Efficacy of treatment with N-acetylcysteine inhalation for AECOPD: A propensity-score-matched cohort study

doi:10.21203/rs.3.rs-1627854/v1

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Efficacy of treatment with N-acetylcysteine inhalation for AECOPD: A propensity-score-matched cohort study

https://doi.org/10.21203/rs.3.rs-1627854/v1

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Background: N-acetylcysteine (NAC) prevents acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the value of N-acetylcysteine (NAC) inhalation in the treatment of an AECOPD requiring hospitalization still remains unclear. The present study was designed to evaluate the clinical efficacy of NAC inhalation in patients with AECOPD requiring hospitalisation.

Methods: In this single-center, retrospective cohort study, all patients with AECOPD requiring hospitalisation between October 2016 and October 2021 were included. The primary outcome was the length of hospital stay. The change in the spirometric parameter, including the post-bronchodilator forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), forced expired flow at 50% of vital capacity (FEF _50%), mean forced expiratory flow between 25% and 75% of vital capacity (FEF _25-75%), residual volume/total lung capacity (RV/TLC), and arterial blood gas tensions over the first 7 days of the admission, the incidence of adverse events (AEs) were calculated to estimate the differences between the two groups.

Results: A total of 1257 patients were enrolled in this study. Of these, 202 propensity score–matched patients (101 in the NAC group and 101 in the Non-NAC group) were included in the final analyses. The mean length of hospital stay was 8.4 days (95% CI 7.6 to 8.4) days for the NAC group and 9.2 days (95% CI 8.6 to 9.4) for the Non-NAC group (p = 0.044). The improvement rates in partial arterial oxygen pressure (P_aO₂),partial pressure of carbon dioxide (P_aCO₂) and spirometric parameter, including FEV₁, FVC, FEF_50%, FEF _25-75%, and RV/TLC were significantly higher in NAC group than in Non-NAC group. No differences between groups were observed in adverse effects, self-reported symptomatic improvement from admision to day 5, mechanical ventilation rates during hospitalization, exacerbation and rehospitalisation rates within one month of discharge.

Conclusion：NAC inhalation can markedly shorten the length of hospital day, improve pulmonary function, raise P_aO₂and decrease P_aCO₂ in patients with AECOPD requiring hospitalization, which may be a safe and effective supplementary treatment in AECOPD patients.

N-acetylcysteine inhalation

AECOPD

Hospitalizations

Clinical efficacy

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic pulmonary diseases and a major public health problem worldwide ^[1]. Acute exacerbations of COPD (AECOPD) are the important cause of emergency hospitalization ^[2] and are associated with significant mortality as well as health and socioeconomic burden ^[3]. Therapeutically, AECOPD are approached as a single entity and treated uniformly with bronchodilators, systemic corticosteroids, and antibiotics ^[4], but optimization management of AECOPD represents an important clinical challenge ^[5].

A series of studies have shown that increased oxidative stress is not only the most important factors in the pathogenesis of COPD ^[6], but also one of the important mechanisms leading to AECOPD ^[7]. Biomarkers associated with oxidative stress such as serum gamma-glutamyltransferase ^[8], 8-Hydroxy-2’- deoxyguanosine ^[9], superoxide dismutase and malondialdehyde levels ^[10] were evidently increased in patients with AECOPD compared with that in healthy subjects and patients with stable COPD. The abnormally elevated oxidative stress can attenuate macrophage function, thus resulting in impaired responses toward exacerbating triggers and contributing to exaggerated inflammation in the airways ^[11]. Therapeutic intervention targeting the oxidative stress may give the possibility to improve the prognosis of patients with AECOPD.

N-acetylcysteine (NAC), a precursor of glutathione and a synthetic derivative of the endogenous amino acid L-cysteine, has been proposed not only as an expectorant, but also as a therapeutic agent in a variety of disorders involving oxidative stress ^[12]. For the past several decades, it is widely used in several lung disorders as a mucolytic ^[13].

Although NAC has been shown to prevent the occurrence of AECOPD ^[14], as well as the pre-clinical data about the use of NAC inhalation in AECOPD indicate a positive efficacy, its therapeutic value in the treatment of AECOPD has yet to be explored in further studies. Accordingly, the purpose of this study is to evaluate the efficacy and safety of NAC inhalation in the treatment of patients with AECOPD requiring hospitalization.

Study design and Patients

This was a single-center, retrospective cohort study. Patients ≥ 50 years of age with a clinical diagnosis of AECOPD requiring hospitalization between January 2021 and January 2022 at Pulmonary and Critical Care Medicine Unit of Seventh People's Hospital of Chongqing were included. The diagnosis of COPD was supported by spirometric evidence of airflow obstruction even with bronchodilator (forced expiratory volume in 1 second/forced vital capacity < 0.70) when clinically stable ^[15]. AECOPD were defined as an acute worsening of respiratory symptoms such as cough, dyspnea, or sputum purulence severe enough to warrant hospitalization ^[15]. All the included patients had a minimum of two arterial blood gas measurements and pulmonary function tests. The first measurement and test time were between 24 h before admission and 24 h after admission. Another measurement and test were conducted between the 5-to-7-day after admission.

Exclusion criteria were the presence of pulmonary embolism, asthma, allergic rhinitis or atopy, interstitial pulmonary disease, advanced lung cancer, active pulmonary tuberculosis or bronchiectasis, acute heart failure, cerebrovascular accident, acute respiratory acidosis needing noninvasive ventilation, serious heart, liver, kidney, gastrointestinal diseases, or endocrine disease; Patients were also excluded from the study if the length of NAC inhalation therapy was less than 5 days, or had been exposed to NAC by oral administration during hospitalization.

The patients were divided into two groups: the AECOPD patients who accepted the treatment of inhaled NAC (Acetylcysteine Solution for Inhalation, 3ml:0.3g, bid) while receiving routine treatment including oxygen therapy, expectorant, bronchodilators, systemic glucocorticoids, antibiotics, expectorant, and fluid rehydration were included in NAC group, and those treated just with routine therapy were included in Non-NAC group. The patient recruitment flow diagram was presented in Fig. 1.

Outcomes Definitions

The primary outcome was the length of hospital stay. Secondary outcomes were the change in the post-bronchodilator forced expiratory volume in one second (FEV ₁) over the first 7 days of the admission, forced vital capacity (FVC), forced expired flow at 50% of vital capacity (FEF _50%), mean forced expiratory flow between 25% and 75% of vital capacity (FEF _25-75%), partial arterial oxygen pressure (P_aO₂), partial pressure of carbon dioxide (P_aCO₂), the dosage of systemic glucocorticoids, the incidence of adverse events (AEs) were calculated to estimate the differences between the two groups.

Statistical analysis

Descriptive statistical methods were used to characterize the sample. All quantitative data were expressed as mean ± SD. The chi-squared test was used to compare discrete variables. ANOVA and paired t-tests were used to compare changes in continuous variables between and within the groups, respectively.

The propensity score match (PSM) used to match patients between the NAC and Non-NAC treatment groups was estimated for each patient with a multivariate logistic regression model using baseline patient characteristics. The PSM was rigorously constructed and implemented according to guidelines ^[16]. The following characteristics of patients were included in the model: sex, age, current smoking status, COPD assessment test (CAT) score, comorbidities, P_aO_2, and P_aCO₂.

The PSM was performed using a 1:1 nearest-neighbor method without replacement, which attempted to match each patient in the NAC group with a patient of the Non-NAC group based on the closest propensity score, with a 0.1 caliper width. Assessment of matching quality was performed with comparing the two groups before and after PSM to check if significant differences in covariate statistics remained after matching.

Statistical analyses were performed using Statistical Package for Social Sciences software, version 26.0 (SPSS, Inc., Chicago, IL, US). A p value of less than 0.05 indicated statistical significance.

Baseline characteristics

A total of 476 patients were included in the analysis (Fig. 1). The baseline characteristics were compared between the NAC group (n = 101) and the Non-NAC group (n = 375), as shown in Table 1. There were no significant differences in most baseline parameters, including sex, body mass index (BMI), current smoking status, time of exacerbation, and pulmonary function. In comparison to the Non-NAC group, patients in the NAC group had higher CAT score (p = 0.000) and P_aCO₂ (p = 0.004). The NAC group were also older than Non-NAC group (p = 0.048). In addition, the NAC group had a higher incidence of ischaemic heart disease (p = 0.039) and TypeⅡrespiratory failure (p = 0.040).

Table 1

Baseline characteristics of hospitalized AECOPD patients before propensity score matching.
Characteristics	Overall population
Characteristics	NAC group (n = 101)	Non-NAC group (n = 375)	P value
Age(yrs)	71.1 ± 8.11	69.3 ± 7.99	0.048
Sex
Male	77(76.2%)	296(78.9%)	0.587
Female	24(23.8%)	79(21.1%)	0.587
BMI(kg/m²)	21.9 ± 1.38	22.2 ± 1.42	0.104
Current smokers	20(19.8%)	71(18.9%)	0.887
Time of exacerbation(d)	7.0 ± 2.94	6.4 ± 2.69	0.050
CAT score	22.7 ± 3.78	20.3 ± 4.48	0.000
P_aO₂ mmHg	68.6 ± 8.43	69.9 ± 10.46	0.244
P_aCO₂ mmHg	49.8 ± 9.92	47.1 ± 8.07	0.004
PH	7.4 ± 0.04	7.4 ± 0.04	0.120
Baseline spirometry
FEV₁%pred	46.2 ± 18.16	46.8 ± 18.41	0.774
FVC%pred	69.8 ± 18.47	71.7 ± 17.48	0.335
FEV₁/FVC(%)	51.8 ± 9.93	50.5 ± 11.32	0.294
FEF_50%pred	16.7 ± 9.73	16.9 ± 8.78	0.807
FEF_{25 − 75%}pred	15.7 ± 8.34	15.9 ± 7.50	0.818
RV/TLC	54.7 ± 7.09	54.3 ± 6.59	0.587
Concomitant medication use, No.(%)
Inhaled corticosteroids	82(81.2%)	327(87.2%)	0.123
Inhaled bronchodilator	94(93.1%)	351(93.6%)	0.848
Theophylline	95(94.1%)	355(94.7%)	0.812
Expectorant	72(71.3%)	359(95.7%)	0.000
Antibiotic	95(94.1%)	361(96.3%)	0.326
Comorbidities
Hypertension	33( 32.7%)	89( 23.7%)	0.070
Type 2 diabetes mellitus	5(5.0%)	20( 5.3%)	1.000
Ischaemic heart disease	40(39.6%)	107(28.5%)	0.039
Pulmonary heart disease	18(17.8%)	75(20.0%)	0.673
TypeⅡRespiratory failure	41( 40.6%)	110( 29.3%)	0.040
Data is presented as mean ± standard deviation. BMI, Body Mass Index; CAT: COPD assessment test; P_aO₂, partial arterial oxygen pressure; P_aCO₂, partial pressure of carbon dioxide; FEV ₁, forced expiratory volume in one second; FVC, forced vital capacity; FEF _50%, forced expired flow at 50% of vital capacity; FEF _25−75%, forced expiratory flow between 25% and 75% of vital capacity; RV/TLC, residual volume/total lung capacity.

We then selected from the entire Non-NAC population, a series of 101 patients matched to the 101 patients in the NAC group through PSM (Table 2). No difference between NAC and Non-NAC groups were observed regarding the age, CAT score, P_aCO₂, as well as comorbidities. Moreover, no difference between groups were detected relative to sex, BMI, current smoking status, time of exacerbation and pulmonary function.

Table 2

Baseline characteristics of hospitalized AECOPD patients in NAC and Non-NAC groups matched by propensity score.
Characteristics	Matched population
Characteristics	NAC group (n = 101)	Non-NAC group (n = 101)	P value	SMD
Age(yrs), mean ± SD	71.1 ± 8.11	71.6 ± 7.00	0.630	-0.02
Sex, No.(%)
Male	77(76.2%)	74(73.3%)	0.746	_
Female	24(23.8%)	27(26.7%)	0.746	_
BMI(kg/m²), mean ± SD	21.9 ± 1.38	21.9 ± 1.54	0.715	-0.05
Current smokers, No.(%)	20(19.8%)	21(20.8%)	1.000	_
Time of exacerbation(d), mean ± SD	7.0 ± 2.94	6.6 ± 2.84	0.382	0.15
CAT score, mean ± SD	22.7 ± 3.78	22.4 ± 4.27	0.519	-0.08
P_aO₂ mmHg, mean ± SD	68.6 ± 8.43	66.1 ± 9.62	0.053	0.15
P_aCO₂ mmHg, mean ± SD	49.8 ± 9.92	50.3 ± 10.05	0.746	-0.14
PH, mean ± SD	7.4 ± 0.04	7.4 ± 0.05	0.554	-0.02
Baseline spirometry, mean ± SD
FEV₁%pred	46.2 ± 18.16	45.3 ± 19.50	0.721	0.01
FVC%pred	69.8 ± 18.47	68.1 ± 18.43	0.517	-0.05
FEV₁/FVC(%)	51.8 ± 9.93	49.7 ± 11.98	0.169	0.16
FEF_50%pred	16.7 ± 9.73	15.4 ± 9.54	0.361	0.01
FEF_{25 − 75%}pred	15.7 ± 8.34	14.8 ± 7.96	0.425	0.06
RV/TLC	54.7 ± 7.09	56.8 ± 7.76	0.052	-0.19
Concomitant medication use, No.(%)
Inhaled corticosteroids	82(81.2%)	84(83.2%)	0.713	_
Inhaled bronchodilator	94(93.1%)	93(92.1%)	0.788	_
Theophylline	95(94.1%)	97(96.0%)	0.517	_
Expectorant	72(71.3%)	76(75.2%)	0.525	_
Antibiotic	95(94.1%)	96(95.0%)	0.757	_
Comorbidities, No.(%)
Hypertension	33(32.7%)	26(25.7%)	0.353	_
Type 2 diabetes mellitus	5(5.0%)	10(9.9%)	0.283	_
Ischaemic heart disease	40(39.6%)	32(31.7%)	0.304	_
Pulmonary heart disease	18(17.8%)	27(26.7%)	0.176	_
TypeⅡRespiratory failure	41( 40.6%)	43( 42.6%)	0.887	_
Data is presented as mean ± standard deviation. SMD, standardized mean difference for continuous variables with normal distribution. Values up to + 0.2 or − 0.2 denote small effect; BMI, Body Mass Index; CAT: COPD assessment test; P_aO₂, partial arterial oxygen pressure; P_aCO₂, partial pressure of carbon dioxide; FEV ₁, forced expiratory volume in one second; FVC, forced vital capacity; FEF _50%, forced expired flow at 50% of vital capacity; FEF _25−75%, forced expiratory flow between 25% and 75% of vital capacity; RV/TLC, residual volume/total lung capacity

Therapeutic effect on clinical outcomes

Table 3

Changes in patient during the course of hospital admission.
	NAC group (n = 101)	Non-NAC group (n = 101)	P value
Length of hospital stay (days), mean ± SD	8.4 ± 2.80	9.2 ± 2.55	0.037
Self-reported symptomatic improvement from admision to day 5, No.(%)	82(81.2%)	77(76.2%)	0.391
Mechanical ventilation rates during hospitalization, No.(%)	3(3.0%)	5(5.0%)	0.471
Exacerbation rates within one month of discharge, No.(%)	14(13.9%)	13(12.9%)	0.836
Rehospitalisation rates within one month of discharge, No.(%)	5(5.0%)	4(4.0%)	0.733
Actual total dose of prednisone (mg) , mean ± SD	305.2 ± 175.5	316.6 ± 133.7	0.604
Data is presented as mean ± standard deviation.

The NAC group was associated with the shorter hospital stay compared with the Non-NAC groups (Table 3). We also analyzed hospitalization days for the NAC and Non-NAC groups using Kaplan-Meier estimates. In the NAC group the mean length of hospital stay was 8.4 days (95% CI 7.6 to 8.4) compared with 9.2 days (95% CI 8.6 to 9.4) for the Non-NAC group (p = 0.044, Fig. 2). There were no significant differences between the two groups with respect to self-reported symptomatic improvement from admission to day 5, mechanical ventilation rates during hospitalization, exacerbation and re-hospitalization rates within 1 month of discharge. Though the average total dose of prednisone equivalent used in the NAC group was slightly lower than the Non-NAC group, there was no significant difference between them.

Compared with the level before treatment, P_aO₂ and spirometric parameter, including FEV₁, FVC, FEV₁/FVC, FEF _50%pred, FEF _25−75%pred and RV/TLC were significantly improved in two groups after 5–7 days, the improvement rates in these parameters were significantly higher in NAC group than in Non-NAC group. Moreover, the mean P_aCO₂ were obviously improved in all AECOPD patients and were better in NAC group than in Non-NAC group (Table 4).

Table 4

Clinical outcomes of hospitalized AECOPD patients after propensity score matching.
Characteristics	Group
Characteristics	NAC group (n = 101)		Non-NAC group (n = 101)
	Baseline	At 5–7 days	Baseline	At 5–7 days
P_aO₂ mmHg, mean ± SD	66.4 ± 10.04	84.3 ± 8.76*^#	68.2 ± 8.00	81.6 ± 8.10*
P_aCO₂ mmHg, mean ± SD	50.8 ± 10.32	44.4 ± 5.60*^#	50.0 ± 9.43	46.1 ± 8.21*
FEV₁%pred, mean ± SD	42.9 ± 18.12	46.2 ± 19.03*^#	45.4 ± 18.49	48.3 ± 21.44*
FVC%pred, mean ± SD	68.5 ± 18.89	70.5 ± 19.07*	70.1 ± 20.13	71.2 ± 20.54*
FEV₁/FVC(%), mean ± SD	48.9 ± 11.22	50.2 ± 11.06*^#	52.2 ± 11.67	52.6 ± 11.76*
FEF_50%pred, mean ± SD	16.2 ± 9.16	20.0 ± 8.98*^#	17.0 ± 10.28	19.8 ± 10.17*
FEF_{25 − 75%}pred, mean ± SD	15.5 ± 8.09	19.6 ± 7.98*^#	16.1 ± 8.74	19.1 ± 8.76*
RV/TLC, mean ± SD	56.1 ± 7.45	50.7 ± 5.87*^#	54.9 ± 7.39	50.3 ± 5.07*
Data is presented as mean ± standard deviation. P_aO₂, partial arterial oxygen pressure; P_aCO₂, partial pressure of carbon dioxide; FEV ₁, forced expiratory volume in one second; FVC, forced vital capacity; FEF _50%, forced expired flow at 50% of vital capacity; FEF _25−75%, forced expiratory flow between 25% and 75% of vital capacity; RV/TLC, residual volume/total lung capacity. *p < 0.05 compared to baseline; ^#p < 0.05 compared to Non-NAC group.

Safety

The incidence of adverse events was similar between groups. While 3 serious adverse events were reported, there was no significant difference in the rate of such events in NAC group (n = 2[2.0%]) and Non-NAC group (n = 1[1.0%]) (Table 5).

Table 5

Summary of adverse events.
	NAC group (n = 101)	Non-NAC group (n = 101)	P value
Treatment-related adverse events, No.(%)
Decreased appetite	14( 13.9%)	16( 15.8%)	0.692
Nausea	11(10.9%)	5(5.0%)	0.118
Constipation	12(11.9%)	10(10.0%)	0.651
Rash	7(6.9%)	9(8.9%)	0.602
Stomatitis	9(8.9%)	8(7.9%)	0.800
Urticaria	3(3.0%)	5(5.0%)	0.471
Severe adverse event, No.(%)	2(2.0%)	1(1.0%)	0.561
Any adverse event, No.(%)	56(55.4%)	53( 52.5%)	0.672

Common treatment-related adverse events included decreased appetite, nausea, constipation, rash, stomatitis and urticaria, the rates of such symptoms did not differ between the NAC and Non-NAC groups, and no serious adverse events were attributed to inhaled N-acetylcysteine. This results indicated that addition of inhaled N-acetylcysteine to routine treatment not substantially alter AECOPD patients’ tolerability.

In the current study, we investigated the efficacy of NAC inhalation for managing patients hospitalised with AECOPD. The results demonstrated that NAC inhalation was related to a shorter hospital stay. Meanwhile, NAC inhalation could markedly improve pulmonary function, raise P_aO₂ and reduce P_aCO₂ without increasing toxicity.

COPD is known to have posed substantial economic and social burden on both patients and healthcare systems ^[17]. In particular, nearly 35–84% of the COPD medical costs are due to AECOPD ^[18]. Also, it has been confirmed that the length of hospital stay is a key indicator of AECOPD patients medical resource use and hospitalization costs ^[19]. Inhalation therapy is the primary way for AECOPD in clinical practice, about 78.2% of AECOPD patients used a combination that mostly involve a ICS and either a long-acting or a short-acting beta-agonist ^[18]. While the benefits of inhaled medication in improving the overall management of COPD have been confirmed ^[3], the use of inhaled medications are found to be associated with a longer length of hospital stay in some study ^[18]. To the best of our knowledge, few studies have evaluated the efficacy of NAC inhalation in AECOPD patients. This report demonstrated the benefit of NAC inhalation on shortening the hospital stay in patients with AECOPD requiring hospitalization. In clinical, it would be an effective supplementary treatment to AECOPD.

It has been reported that taking orally high-dose NAC significantly improved lung function in patients with stable COPD ^[20]. In this study, although initial spirometric parameters were similar between the two groups, the improvement of FEV₁, FEV₁/FVC and RV/TLC in the NAC group was significant higher than that in the Non-NAC group. In addition, FEF _50% and FEF _25−75% for the NAC group at 5–7 days was significantly improved compared to the Non-NAC group, along with the significant improvement of blood gas analysis index. It suggested that NAC inhalation might have played roles in improving lung function of patients with AECOPD during a short-term. Mechanisms of improved lung function by NAC inhalation may be regulation of oxidative stress, inhibition of airway inflammation and reduction of mucus hypersecretion. First, it was reported that pro-inflammatory factors and oxidative stress markers are noticeably overexpressed in acute exacerbation stage compared with those in stable stage for COPD patients, which are negatively related to FEV₁ and FEV₁/FVC, and seem to be associated with increased inflammation and airway remodeling ^[21]. NAC can not only modulate oxidative stress but also other pathophysiologic processes including mitochondrial dysfunction, apoptosis, and inflammation ^[22] so as to ameliorate pulmonary function. Mucus hypersecretion is a distinguishing pathophysiological feature of COPD ^[23], which contributes to lung function impairment observed in COPD ^[24]. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity ^[22], as well as contributing to improvement of pulmonary function. In addition, viral or bacterial respiratory infections are a common cause of AECOPD ^[25], NAC can not only decrease virus titers and inhibit viral proliferation ^[26], but also affect bacterial biofilm formation ^[27], it may also partially explained why NAC inhalation shortened the hospitalization days and improved pulmonary function.

Studies have found that after taking NAC, patients with AECOPD can effectively reduce their symptoms of cough, sputum, and dyspnea ^{[28, 29]}. Because of the ability of alleviating the inflammatory response and injury to the lungs, NAC inhalation showed a tendency to reduce the incidence of postoperative pulmonary complications following orthotopic liver transplantation ^[30]. But there is still a lack of research of NAC inhalation in AECOPD. Results of this study illustrated that self-reported symptomatic improvement from admission to day 5 in NAC groups were higher than in Non-NAC group, but the differences were not statistically significant. As all patients in this study were received adequate therapy including symptomatic treatment, the benefit of NAC inhalation mainly stemmed from anti-oxidation and anti-inflammatory effects, but not from expectorant action of NAC. Zheng JP et al ^[14] reported that consuming NAC orally was associated with a reduced risk of exacerbations in COPD

Patients. But in the study, there was no difference between the two groups in exacerbation and re-hospitalization rates within 1 month of discharge. It suggested that the treatment courses of NAC inhalation should be extended to play the sustained role of anti-oxidation and anti-inflammatory.

Compared with intravenous or oral administration, inhalation medication is delivered by special inhalation device via which that can directly and rapidly act on airways to allow high local drug concentrations and reduce systemic influence. Inhalant NAC solutions has good compatibility with other agents ^[31], and therefore is expected to be well tolerated. Indeed, our study did not demonstrate additional adverse effects with NAC inhalation. The results indicated that NAC inhalation was well tolerated in patients with AECOPD.

Our study also has limitations. This retrospective study was conducted in a single unit with short follow-up time. Further multicenter clinical research with larger sample of patients and longer follow-up times are needed to better understand the use of NAC inhalation in AECOPD as well as to understand its mechanism of action. Furthermore, whether lengthen the course of NAC inhalation could decrease the readmission rate needs further investigation.

In conclusion, in patients with AECOPD, NAC inhalation shortened the hospitalized time, rapidly improved pulmonary function and arterial blood gases.

NAC	N-acetylcysteine
COPD	Chronic obstructive pulmonary disease
AECOPD	Acute exacerbations of chronic obstructive pulmonary disease
FEV₁	Forced expiratory volume in one second
FVC	Forced vital capacity
FEF _50%	Forced expired flow at 50% of vital capacity
FEF _25-75%	Forced expiratory flow between 25% and 75% of vital capacity
RV/TLC	Residual volume/total lung capacity
AEs	Adverse events
P_aO₂	Partial arterial oxygen pressure
P_aCO₂	Partial pressure of carbon dioxide
PSM	Propensity score match
CAT	COPD assessment test
BMI	Body mass index
RV/TLC	Residual volume/total lung capacity
AEs	Adverse events

Ethics approval and consent to participate

The study was approved by the Ethical Committee of the Seventh People’s Hospital of Chongqing. The study is conducted according to the Declaration of Helsinki. Informed consent to participate is not applicable in this retrospective study and is waived by the Ethical Committee of the Seventh People’s Hospital of Chongqing.

Consent for publication

Not applicable.

Availability of data and materials

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

Competing interests

There are no conflicts of interest.

Funding

This study was supported by grants from the Social Undertakings and Livelihood Security Special Projects, the Science and Technology Bureau of Banan District, Chongqing (Grant number: 2021-55).

Authors’ contributions

CHY, ZH, LC and ZKC contributed to the study conception and design. LCY, DY and LTL acquired the data. CHY, ZKC, FYY, LW and XGJ analyzed and interpreted the clinical data. JYZ is responsible for data quality control. CHY and ZKC drafted the manuscript. All authors read and approved the final manuscript.

Acknowledgements

None.

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No competing interests reported.

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Efficacy of treatment with N-acetylcysteine inhalation for AECOPD: A propensity-score-matched cohort study

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