A retrospective analysis of risk factors for massive hemoptysis in patients with bronchiectasis 1

doi:10.21203/rs.3.rs-1445113/v1

Background: Massive hemoptysis is a common and fatal complication of bronchiectasis. However, the risk factors for massive hemoptysis in patients with bronchiectasis have not yet been reported. This study investigated the potential risk factors for massive hemoptysis in patients with bronchiectasis.

Methods: This retrospective study included patients with bronchiectasis and their data were obtained from medical records. The risk factors for massive hemoptysis were evaluated by multivariate analysis of patient characteristics, medical history, and computed tomography imaging data, including the number of lesions, lesion location, and laboratory findings.

Results: Among 379 patients, 61 (16.09%) experienced severe hemoptysis. Multivariate analysis revealed that diabetes (odds ratio (OR), 2.885; 95% confidence interval (CI), 1.009–8.247), lesions involving two lobes (OR, 4.347; 95% CI, 1.960–9.638) and three lobes (OR, 2.787; 95% CI, 1.055–7.363) were significant predictors of severe hemoptysis. However, a disease course between 1 and 5 years (OR, 0.300; 95% CI, 0.112–0.801) and involvement of the left lower lobe (OR, 0.394; 95% CI, 0.196–0.793) were protective factors for the prevention of massive hemoptysis. Lesions in the right upper lobe were more likely to cause massive hemoptysis (OR, 1.458) than involvement of other lobes.

Conclusions: Diabetes and lesions involving two and three lobes, were risk factors for massive hemoptysis in patients with bronchiectasis. Disease duration between 1 and 5 years and involvement of the left lower lobe were protective factors, while lesions in the right upper lobe had a stronger relationship with massive hemoptysis in patients with bronchiectasis.

Bronchiectasis

massive hemoptysis

risk factors

Bronchiectasis is a chronic airway disease characterized by irreversible bronchial dilatation [1, 2]. Patients with bronchiectasis often develop chronic respiratory symptoms, including productive sputum, chronic cough, hemoptysis, dyspnea, and recurrent infection [1]. Massive hemoptysis is a life-threatening condition with high mortality rates [3, 4]. Bronchiectasis is one of the most common causes of massive hemoptysis [5]. The risk factors for severe hemoptysis in patients with bronchiectasis are not well known. Therefore, this study aimed to investigate the potential risk factors associated with massive hemoptysis in patients with bronchiectasis.

Study population

We retrospectively analyzed the medical records of patients with bronchiectasis from the University Town Hospital of Chongqing Medical University in Chongqing, China. Clinical data for 379 patients diagnosed with bronchiectasis between January 1, 2014, and June 30, 2021, were obtained. Bronchiectasis was diagnosed by typical chest computed tomography (CT) scan features: an abnormally widened and thickened airway with an irregular wall, lack of tapering, and/or visibility of the airway in the periphery of the lung [6]. The study was approved by the institutional review board of University-town hopspital of Chongqing medical university and the requirement for informed consent was waived because of the retrospective nature of the study.

Potential risk factors:

Potential variables including the following patient characteristics at hospital admission were obtained: clinical course, history of bronchial artery embolism, and previous history of massive hemoptysis, demographic variables, medical history, imaging features, and laboratory findings. Demographic variables collected for the study included age (< 40 years, ≥ 40 and < 50 years, ≥ 50 and < 60 years, ≥ 60 and < 70 years, ≥ 70 years), sex (male and female), and smoking status (never, current, and former). Medical history including the disease course (≤ 1 year, > 1 and ≤ 5 years, > 5 and ≤ 10 years, > 10 years), presence of complications (chronic obstructive pulmonary disease, diabetes, hypertension, pulmonary fungus, and pneumonia), and the use of aspirin and anticoagulation, were obtained. Imaging features collected included the locations of abnormalities in the chest computed tomography (CT) imaging. Laboratory findings including platelet counts and D-dimer levels were obtained.

Massive hemoptysis definitions:

Massive hemoptysis was defined based on the Chinese Expert Recommendation for Diagnosis and Treatment of Massive Hemoptysis, given the extensive acceptance of this guideline [7]. Hemoptysis of blood > 500 ml within 24 h, or > 100 ml within one hour, or > 100 ml in each episode of hemoptysis was considered as massive hemoptysis. Moreover, any life-threatening hemoptysis and any hemoptysis that may cause airway obstruction and asphyxia were also considered as massive hemoptysis [8, 9].

Statistical methods:

The data were double-checked before entry into the computer. Mean differences between the two groups were evaluated by univariate analysis (Pearson chi-squared test, calibration chi-squared test, and Fisher’s exact test for categorical variables). Multivariate logistic regression analysis based on AIC regulations was performed for factors found to have a P-value < 0.05 in the univariate analysis, to identify the risk factors of massive hemoptysis in patients with bronchiectasis. The risk factors were presented as odds ratios (ORs) with a 95% confidence interval (CI). Subsequently, the independent factors were taken as control variables, and five different lobes were included to observe their different risks for massive hemoptysis. Statistical analyses were performed using SPSS version 26.0, and statistical significance was set at P < 0.05.

Of the 379 patients with bronchiectasis, 61 had massive hemoptysis, of whom 40 (20.3%) were male. Most patients were between 60 and 70 years of age, but 18 (19.15%) patients who had massive hemoptysis were more than 70 years. Current smoking patients had a higher incidence (25%) of massive hemoptysis. A total of 124 (32.72%) patients were diagnosed with bronchiectasis less than one year prior, of whom 27 (21.77%) had massive hemoptysis. Three patients received anticoagulation, and one of them had severe hemoptysis. Three (33.3%) patients had pulmonary fungal complications. Eighty-seven patients had pulmonary lesions in two lobes and the incidence of massive hemoptysis among them was 27.59%.

In the univariate analysis, massive hemoptysis was more likely to occur in patients who had not stopped smoking (P = 0.028). It was less likely to occur in women (P = 0.022) and in patients with disease course between 1 and 5 years (P = 0.016). Massive hemoptysis was also more likely to occur when lesions involved two lobes (P = 0.004); however, patients whose lesions were located in the left lower lobes were less likely to develop massive hemoptysis (P = 0.03) (Table 1).

Multivariate analysis revealed that the presence of diabetes (OR, 2.885; 95% CI, 1.009–8.247; P = 0.048), lesions in two lobes (OR, 4.347; 95% CI, 1.960–9.638; P < 0.001), and lesions in three lobes (OR, 2.787; 95% CI, 1.055–7.363; P = 0.039) were significantly associated with massive hemoptysis (Table 2). It also revealed that a disease course between 1 and 5 years (OR, 0.300; 95% CI, 0.112–0.801; P = 0.016) and involvement of left lower lobe (OR, 0.394; 95% CI, 0.196–0.793; P = 0.009) were protective factors for the prevention of massive hemoptysis. We considered these risk factors as control variables and found that lesions in the right upper lobe were more likely to cause massive hemoptysis (OR, 1.458), while lesions in the left lower lobe were less likely to cause massive hemoptysis (OR, 0.550) (Table 3).

Table 1

Univariate analysis for the association between potential risk factors and massive hemoptysis among patients with bronchiectasis
	Massive hemoptysis			P (χ2)	OR (95% CI)	P (OR)
	Total (n = 379)	No (n = 318)	Yes (n = 61)
Gender				0.020*
Male	197 (51.98)	157 (79.70)	40 (20.30)		ref.
Female	182 (48.02)	161 (88.46)	21 (11.54)		0.512 (0.289, 0.907)	0.022*
Age (years)				0.915
< 40	23 (6.07)	19 (82.61)	4 (17.39)		ref
(40,50)	61 (16.09)	52 (85.25)	9 (14.75)		0.822 (0.226, 2.986)	0.766
(50,60)	93 (24.54)	79 (84.95)	14 (15.05)		0.842 (0.249, 2.848)	0.782
(60,70)	108 (28.50)	92 (85.19)	16 (14.81)		0.826 (0.248, 2.748)	0.755
≥ 70	94 (24.80)	76 (80.85)	18 (19.15)		1.125 (0.341, 3.714)	0.847
Smoking				0.073
Never	277 (73.09)	238 (85.92)	39 (14.08)		ref.
Current	72 (19.00)	54 (75.00)	18 (25.00)		2.034 (1.081, 3.826)	0.028*
Former	30 (7.92)	26 (86.67)	4 (13.33)		0.939 (0.311, 2.837)	0.911
Course (years)				0.075
≤ 1	124 (32.72)	97 (78.23)	27 (21.77)		ref.
(1,5]	74 (19.53)	68 (91.89)	6 (8.11)		0.317 (0.124, 0.809)	0.016*
(5,10]	74 (19.53)	61 (82.43)	13 (17.57)		0.766 (0.367, 1.597)	0.476
༞10	107 (28.23)	92 (85.98)	15 (14.02)		0.586 (0.293, 1.171)	0.130
PTMH				0.242
No	357 (94.20)	302 (84.59)	55 (15.41)		ref.
Yes	22 (5.80)	16 (72.73)	6 (27.27)		2.059 (0.772, 5.493)	0.149
Hypertension				0.334
No	320 (84.43)	271 (84.69)	49 (15.31)		ref.
Yes	59 (15.57)	47 (79.66)	12 (20.34)		1.412 (0.699, 2.853)	0.336
Diabetes				0.154
No	359 (94.72)	304 (84.68)	55 (15.32)		ref.
Yes	20 (5.28)	14 (70.00)	6 (30.00)		2.369 (0.873, 6.430)	0.091
COPD				0.658
No	306 (80.74)	258 (84.31)	48 (15.69)		ref.
Yes	73 (19.26)	60 (82.19)	13 (17.81)		1.165 (0.594, 2.285)	0.658
Asprin				1.000
No	366 (96.57)	307 (83.88)	59 (16.12)		ref.
Yes	13 (3.43)	11 (84.62)	2 (15.38)		0.946 (0.204, 4.378)	0.943
Anticoagulation				0.410
No	376 (99.21)	316 (84.04)	60 (15.96)		ref.
Yes	3 (0.79)	2 (66.67)	1 (33.33)		2.633 (0.235, 29.504)	0.432
Pulmonary fungus				0.334
No	370 (97.63)	312 (84.32)	58 (15.68)		ref.
Yes	9 (2.37)	6 (66.67)	3 (33.33)		2.690 (0.654, 11.060)	0.170
Pneumonia				0.658
No	306 (80.74)	258 (84.31)	48 (15.69)		ref.
Yes	73 (19.26)	60 (82.19)	13 (17.81)		1.165 (0.594, 2.285)	0.658
PLT (x10⁹/L)				0.698
Normal	317 (83.64)	268 (84.54)	49 (15.46)		ref.
Low	44 (11.61)	35 (79.55)	9 (20.45)		1.406 (0.636, 3.109)	0.399
High	18 (4.75)	15 (83.33)	3 (16.67)		1.094 (0.305, 3.920)	0.890
D-dimer (mg/L)				0.620
Normal	276 (72.82)	230 (83.33)	46 (16.67)		ref.
High	103 (27.18)	88 (85.44)	15 (14.56)		0.852 (0.453, 1.604)	0.620
Lobes				0.012 *
1	128 (33.77)	113 (88.28)	15 (11.72)	A	ref.
2	87 (22.96)	63 (72.41)	24 (27.59)	B	2.870 (1.404, 5.866)	0.004**
3	59 (15.57)	49 (83.05)	10 (16.95)	Ab	1.537 (0.646, 3.661)	0.331
4	31 (8.18)	29 (93.55)	2 (6.45)	Ab	0.520 (0.112, 2.401)	0.402
5	74 (19.53)	64 (86.49)	10 (13.51)	Ab	1.177 (0.500, 2.773)	0.709
Left upper lobe				0.732
No	185 (48.81)	154 (83.24)	31 (16.76)		ref.
Yes	194 (51.19)	164 (84.54)	30 (15.46)		0.909 (0.525, 1.572)	0.732
Left lower lobe				0.029*
No	128 (33.77)	100 (78.12)	28 (21.88)		ref.
Yes	251 (66.23)	218 (86.85)	33 (13.15)		0.541 (0.310, 0.943)	0.030*
Right upper lobe				0.137
No	237 (62.53)	204 (86.08)	33 (13.92)		ref.
Yes	142 (37.47)	114 (80.28)	28 (19.72)		1.518 (0.873, 2.640)	0.139
Right middle lobe				0.595
No	187 (49.34)	155 (82.89)	32 (17.11)		ref.
Yes	192 (50.66)	163 (84.90)	29 (15.10)		0.862 (0.498, 1.491)	0.595
Right lower lobe				0.801
No	192 (50.66)	162 (84.38)	30 (15.62)		ref.
Yes	187 (49.34)	156 (83.42)	31 (16.58)		1.073 (0.620, 1.856)	0.801
Note: * p < 0.05, p < 0.01, * p < 0.001; PTMH: previous times of massive hemoptysis; COPD: chronic obstructive pulmonary disease; PLT: platelet

Table 2

Results of multivariate analysis to determine the influencing factors for massive hemoptysis among patients with bronchiectasis
Variable	OR	95% CI	P value
Gender
Male	ref
Female	0.565	0.307–1.043	0.068
Course(years)
≤ 1	ref
(1,5]	0.3000	0.112–0.801	0.016
(5,10]	0.850	0.382–1.890	0.690
༞10	0.784	0.357–1.724	0.545
Diabetes
No	ref
Yes	2.885	1.009–8.247	0.048
Lobes
1	ref
2	4.347	1.960–9.638	< 0.001
3	2.787	1.055–7.363	0.039
4	1.017	0.201–5.137	0.984
5	2.431	0.844–6.999	0.100
Left lower lobe
No	ref
Yes	0.394	0.196–0.793	0.009
CI = confidence interval; Ref = reference; OR = odd ratio

Table 3

The relationship between the involvement of different pulmonary lobes and massive hemoptysis in patients with bronchiectasis
	Variable	Se	z	Wald	p	OR (95% CI)
Controlling factors	(Intercept)	0.326	-3.140	9.858	0.002
	Gender
	Male
	Female	0.308	-1.958	3.833	0.050	0.547 (0.300, 1.001)
	Course (years)
	≤ 1	0.494	-2.064	4.262	0.039	0.361 (0.137, 0.950)
	(1,5]	0.408	-0.586	0.343	0.558	0.787 (0.354, 1.751)
	(5,10]	0.400	-0.844	0.712	0.399	0.713 (0.325, 1.563)
	༞10	0.494	-2.064	4.262	0.039	0.361 (0.137, 0.950)
	Diabetes
	No
	Yes	0.531	1.840	3.387	0.066	2.655 (0.939, 7.512)
Independent variable-s	Left upper lobe
	No
	Yes	0.325	0.141	0.020	0.888	1.047 (0.554, 1.978)
	Left lower lobe
	No
	Yes	0.320	-1.865	3.476	0.062	0.550 (0.294, 1.031)
	Right upper lobe
	No
	Yes	0.315	1.196	1.430	0.232	1.458 (0.786, 2.704)
	Right middle lobe
	No
	Yes	0.332	-0.496	0.246	0.620	0.848 (0.443, 1.625)
	Right lower lobe
	No
	Yes	0.338	0.733	0.538	0.463	1.281 (0.661, 2.484)

In this retrospective study, we investigated the risk factors for massive hemoptysis in patients with bronchiectasis and found that the presence of diabetes, lesions in two lobes, and involvement of the left lower lobe were associated with severe hemoptysis. However, this study also revealed that shorter disease courses (between 1 and 5 years) and patients with lesions involving the left lower lobe had a lesser chance of developing massive hemoptysis.

The most common causes of massive hemoptysis include bronchiectasis, tuberculosis, lung cancer, necrotizing pneumonia, and cryptogenic hemoptysis [8, 10]. There have been no reports on the incidence of massive hemoptysis in patients with bronchiectasis. In the present study, massive hemoptysis occurred in 16.09% of patients with bronchiectasis. In a previous survey, the prevalence of bronchiectasis was higher in elderly patients and women in Taiwan [11]; however, there was no significant difference in the incidence of severe hemoptysis between males and females, as well as among the different age groups in the present study.

Emerging evidence suggests that diabetic patients frequently report respiratory symptoms [12, 13] and are at an increased risk for several respiratory diseases [14–16]. However, bronchiectasis was not observed. We observed that diabetes was a risk factor for severe hemoptysis in patients with bronchiectasis. Animal studies suggest that diabetes may have a direct effect on the pulmonary vasculature. Pulmonary arteries from diabetic rats have been reported to be less responsive to vasodilatation because of increased endothelial dysfunction [17]. Pulmonary vasculature may be affected by diabetic microvascular and macrovascular injuries [13]. Hyperglycemia can lead to complicated infections in the lungs, such as tuberculosis, fungal, and non-tuberculous mycobacterial infections, which can cause massive hemoptysis.

The number of lobes involved by the lesions was found to be an independent predictor of massive hemoptysis in patients with bronchiectasis. We observed that the involvement of two lobes was a significant risk factor. Patients with lesions in the right upper lobe were more likely to develop massive hemoptysis. An interesting finding of our study was that lesions located in the left lower lobe rarely caused hemoptysis. In a long-term follow-up study of bronchial artery embolization for massive hemoptysis, the right bronchial artery was found to be the artery most responsible for bleeding [18]. Another previous study found that the right bronchial artery was responsible for hemoptysis in patients with bronchiectasis [19]. The right lobe is supplied by the right bronchial artery. This might be the reason for higher risk with right lobe involvement. However, why the right upper lobe was not a risk factor is still unknown. Therefore, further studies should be conducted on this topic. At present, the reasons for the lower incidence of massive hemoptysis in the left lower lobe are unclear. No studies have been conducted on this topic. There are also few reliable reports that could explain why the number of two or three lesion lobes was a risk factor for massive hemoptysis. Future prospective studies will be designed to assess the relationship between the number of lesion lobes and massive hemoptysis.

Nonbronchial systemic arteries such as the subclavian, internal mammary, and intercostal arteries, can be a significant source of massive hemoptysis [20]. It may take a longer time for abnormal vessels to develop in patients with bronchiectasis; therefore, patients with disease courses between one and five years may develop severe hemoptysis. However, this needs to be confirmed by clinical evidence.

The limitations of this study are as follows: first, this was a retrospective study performed at only one hospital with a small number of patients with bronchiectasis, who were from the same region. Additional studies should be conducted in other regions to evaluate the risk factors for massive hemoptysis. Second, hemoptysis could not be quantified because the degree and extent of hemoptysis were rarely described in the medical records. In addition, not all laboratory findings and complications were included as potential risk factors; therefore, some risk factors might have been missed in this study. More studies on the risk factors for massive hemoptysis in patients with bronchiectasis are warranted.

In this study, we showed that the presence of diabetes, lesions involving two lobes, and lesions involving three lobes were significant risk factors for massive hemoptysis in patients with bronchiectasis. Patients whose disease course was between 1 and 5 years and whose pulmonary lesions were located in the left lower lobe were less likely to develop massive hemoptysis. Lesions in the right upper lobe had a stronger relationship with massive hemoptysis than other lobes.

Author information

Ling Luo^1† and Jing Luo^1† have contributed equally as first author to this study.

*Corresponding author: Yu Jiang

Affiliation

Department of Respiratory and Critical Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China

Ling Luo, Jing Luo, Yu Jiang

Author information

Ling Luo^1† and Jing Luo^1† have contributed equally as first author to this study.

*Corresponding author: Yu Jiang

Affiliation

Department of Respiratory and Critical Medicine, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China

Ling Luo, Jing Luo, Yu Jiang

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki, which was revised in 1983.The study was approved by the institutional review board of University-town hopspital of Chongqing medical university and all patients information in this study was handled anonymously , meanwhile because of the retrospective nature of the study, informed consent was therefore waived in University-town hopspital of Chongqing medical university.

Consent for publication

Not applicable

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing interests

The authors declare no conflicts of interests.

Funding

None

Author’s contributions

Ling Luo and Jing Luo contributed equally to data collection, data analysis, manuscript drafting, and literature research. Yu Jiang revised the manuscript for important intellectual content. All authors have read and approved the final manuscript.

Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

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No competing interests reported.

massivehemoptysisinbronchiectasis.xls

A retrospective analysis of risk factors for massive hemoptysis in patients with bronchiectasis 1

Status:

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Abstract

Introduction

Materials And Methods

Study population

Potential risk factors:

Massive hemoptysis definitions:

Statistical methods:

Results

Discussion

Conclusions

Author information

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1