Mortality and Prognostic Factors for Spontaneous Pneumothorax in Older Adults: A Retrospective Study

doi:10.21203/rs.3.rs-2622853/v1

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Mortality and Prognostic Factors for Spontaneous Pneumothorax in Older Adults: A Retrospective Study

https://doi.org/10.21203/rs.3.rs-2622853/v1

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Background

Spontaneous pneumothorax occurs predominantly in young males and older adults, in whom it is often secondary to chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILDs) and can be refractory and fatal. We aimed to investigate the mortality and prognostic factors for pneumothorax in older patients.

Methods

We retrospectively studied patients with pneumothorax aged ≥ 65 years who visited our department from October 2012 to January 2019. Data on sex, age, medical history, smoking history, underlying lung disease, treatment, and prognosis were extracted from the medical records. Cox proportional hazards regression analysis was used to investigate pneumothorax mortality and prognostic factors.

Results

A total of 239 patients were included (median age, 78 years; 203 males and 36 females). Thirty-six patients (15%) died during hospitalisation, respiratory disease was the direct cause of death in 30 patients (83.3%), and 211 (88.3%) patients had underlying lung disease. The incidence of pneumonia in our hospital was 22.6% (54 cases), higher than previous reports (11%). On admission, the mortality rate was 33% (18/54) in patients with concomitant pneumonia; univariate analysis showed significant differences in the Charlson Comorbidity Index (CCI), activities of daily living (ADL), and concomitant pneumonia. Cox proportional hazard regression analyses for ADL, CCI, and concomitant pneumonia showed that concomitant pneumonia was the only independent predictor of death during hospitalisation (log-rank, p = 0.005).

Conclusion

Although COPD and ILDs are generally considered as mortality risks for pneumothorax, this study suggests that concomitant pneumonia at admission may be a mortality risk factor for pneumothorax.

Spontaneous pneumothorax

older adults

pneumonia

mortality

Spontaneous pneumothorax, also known as primary spontaneous pneumothorax (PSP), most commonly occurs in young people with no underlying pulmonary disease. In older adults, it is secondary to chronic obstructive lung disease (COPD), cystic fibrosis, pneumocystis pneumonia, lung cancer, and interstitial lung diseases (ILDs). In a study of pneumothorax in older adults in Japan, 90% had underlying lung disease,¹ referred to as secondary spontaneous pneumothorax (SSP).^2,3 SSP is a potentially life-threatening disease because of impaired lung function or general condition, due to underlying lung disease. The presence of underlying lung disease often makes pneumothorax more refractory and difficult to treat, thus prolonging hospitalisation and decreasing activities of daily life (ADL). Onuki et al. reported that the mortality rate of 751 patients with spontaneous pneumothorax was 1.7%, of which 4.6% (266) were SSP patients.⁴ They reported that emphysema was the most frequent cause of death in SSP patients. However, to the best of our knowledge, there are no reports in Japan on the prognostic factors of spontaneous pneumothorax in the older population. Japan's super-ageing society and the need to consider palliative management based on the patient's underlying disease and general condition necessitate this study. This study aimed to investigate the mortality and prognostic factors of spontaneous pneumothorax in older adults.

Patients

Consecutive patients aged ≥ 65 years with spontaneous pneumothorax who visited our department from October 2012 to January 2019 were retrospectively studied. The Institutional Review Board of Iizuka Hospital approved this study for Clinical Research (approval no. 21085).

Data and statistical analyses

Data extracted from the medical records included age, sex, smoking status, ADL before admission (complete independence, total assistance, and others), history of pneumothorax, regular use of systemic corticosteroids, use of home oxygen therapy, time from the onset of pneumothorax to a hospital visit, comorbidities, length of hospitalisation, management of pneumothorax, length of chest tube placement, intensive care unit admission, and survival. In addition, chest radiographs on admission were reviewed, and the size of the pneumothorax was classified according to the criteria of: the Japan Society for Pneumothorax and Cystic Lung Diseases,⁵ the American College of Chest Physicians,⁶ and the British Thoracic Society.⁷ Management of pneumothorax included observation, needle aspiration, chest tube drainage, chemical pleurodesis, surgery, thoracographic fibrin glue sealing method, and endobronchial Watanabe spigot placement, with some patients receiving multiple treatments.

We conducted a retrospective descriptive study based on the medical records. All statistical analyses were performed using the EZR,⁸ a modified version of R commander designed to add statistical functions frequently used in biostatistics. The baseline characteristics were analysed using descriptive statistics. Mann–Whitney’s U and Fisher's exact tests were used to compare patient characteristics and treatment outcomes. Categorical variables were described as frequencies and percentages. Continuous variables with standard distributions were represented as median and standard derivations. We divided the participants into in-hospital death and survival groups. Univariate analysis was performed on the data extracted from the medical records. Cox proportional hazards regression analysis was performed on the univariate analyses that were significantly different, and we developed a Kaplan‒Meier survival model.

Patient characteristics

Table 1 shows the patients' clinical characteristics and a comparison of the survival and in-hospital mortality groups. A total of 239 patients (203 males and 36 females) with a median age of 79 years were included in the analysis. Of the 239 patients, 225 (94.1%) were hospitalised, and 36 (15.1%) died during hospitalisation. Forty-six patients (19.2%) had a history of at least one pneumothorax event. There was a trend towards a slightly older age in the in-hospital death group compared with that in the survivor group (median age, 81 vs. 79, p = 0.08). No sex differences were observed between the two groups (p = 0.62). There was no statistically significant difference in smoking history and smoking status between the survival and in-hospital death groups (p = 0.89 for both). There was a statistically significant difference in ADL between the two groups, with more patients requiring some form of assistance in the in-hospital death group (p = 0.02). The number of patients with a history of pneumothorax was higher in the survival group (p < 0.01), and there was no significant difference between the two groups in the rate of regular systemic steroid use (p > 0.05). The use of home oxygen therapy tended to be slightly higher in the in-hospital death group (p = 0.08), and the Charlson Comorbidity Index (CCI) was significantly higher in the in-hospital death group (p < 0.01). There were no statistically significant differences between the two groups in terms of the time from the onset of pneumothorax to the hospital visit (p = 0.10), the number of hospitalised patients (p = 0.14), and length of hospitalisation (p = 0.75). The length of chest tube placement and intensive care unit admission rates were significantly longer and higher in the in-hospital death group (p = 0.02 and p = 0.03, respectively).

Table 1

Patient characteristics (N = 239)
Characteristics		Total (N = 239)	In-hospital death			P-value
Characteristics		Total (N = 239)	- (N = 203)	+ (N = 36)		P-value
Age, Years		79 (72–85)	79 (71–84)	81 (76–87)		0.08
Sex	Male Female	203 (84.9) 36 (15.6)	171 (84.2) 32 (15.8)	32 (88.9) 4 (11.1)		0.62
Smoking history, pack-year		40 (2–60)	20 (13–60)	35 (5–63)		0.89
Smoking status	Current smoking Formerly smoked Never smoked Unknown	28 (11.7) 148 (61.9) 54 (22.6) 9 (3.8)	25 (12.4) 125 (62.2) 46 (22.9) 7 (3.5)	3 (8.3) 23 (63.9) 8 (22.2) 2 (5.6)		0.89
Activities of daily living	Complete Independence Total assistance Other	158 (66.1) 40 (16.7) 41 (17.2)	141 (69.5) 29 (14.3) 33 (16.3)	17(47.2) 11 (30.6) 8 (22.2)		0.02
Past history of pneumothorax		46 (19.2)	45 (22.2)	1 (2.8)		< 0.01
Systemic corticosteroid use		31 (13.0)	27 (13.1)	4 (11.1)		1
Home oxygen therapy		26 (10.9)	19 (9.4)	7 (19.4)		0.08
Time from onset of pneumothorax to hospital visit, days		0 (0)	0 (0–1)	0 (0)		0.10
Charlson Comorbidity Index		2 (1–4)	2 (1–3)	3 (2–5)		< 0.01
Hospitalised patients		225 (94.1)	189 (93.1)	36 (100)		0.14
Length of hospitalisation, days		21 (11–33)	21 (11–31)	22 (9–42)		0.75
Length of chest tube placement, days		10 (1–11)	6 (1–10.5)	9 (2.75–17.5)		0.02
ICU admission		2 (0.8)	0 (0)	2 (5.6)		0.03
CAUSES OF DEATH Pneumonia ILD COPD Pneumothorax Lung cancer Heart failure Other					16 (44.4) 6 (16.7) 3 (8.3) 2 (5.5) 2 (5.5) 2 (5.5) 5 (13.9)
Age, smoking history, time from onset of pneumothorax to hospital visit, Charlson Comorbidity Index, and length of hospitalisation are presented as median (interquartile range). All the other data are presented as the number of patients (percentage of all patients).
COPD: chronic obstructive pulmonary disease, ILD: interstitial lung disease.

Cause of death

Thirty-six patients (15.1%) died during hospitalisation. Table 1 shows the cause of death determined for the 36 patients according to the direct cause recorded on the death certificate and summary. The causes of death were as follows: pneumonia, 16 patients (44.4%); ILD, six patients (16.7%); COPD, three patients (8.3%); pneumothorax, three patients (8.3%); lung cancer, two patients (5.5%); heart failure, two patients (5.5%); and other, five patients (13.9%). Respiratory disease was the cause of death in 30 patients (83.3%). Patients were admitted with pneumothoraces, but many died because of deterioration of the underlying lung disease.

Underlying lung diseases

Table 2 summarises the underlying lung diseases. Only 28 (11.7%) patients had no underlying lung disease. A wide variety of underlying lung diseases were observed (emphysema, ILD, lung cancer, aspergillosis, asthma, tuberculosis, nontuberculous mycobacteriosis, pneumoconiosis, bronchiectasis, metastatic lung tumour, and Birt–Hogg–Dubé syndrome), but the frequency of these diseases did not differ significantly between the survival and in-hospital death groups. However, the frequency of comorbid pneumonia on admission was higher in the death group than that in the survival group (50.0% vs. 17.7%, p < 0.01).

Table 2

Underlying lung diseases
Underlying lung diseases			Total N = 239		In-hospital death				P-value
					- (N = 203)		+ (N = 36)
None			28 (11.7)		24 (11.8)		4 (11.1)		1
Emphysema	Emphysema only			94 (39.3)		82 (40.4)		12 (33.3)		0.46
	+ ILD	only		21 (8.8)		17 (8.4)		4 (11.1)		0.53
		+ Lung cancer		2 (0.8)		1(0.5)		1(2.8)		0.28
		+ Aspergillosis		1 (0.4)		1 (0.5)		0 (0)		1
		+ Asthma		1 (0.4)		1 (0.5)		0 (0)		1
		+ Chronic Tuberculosis		1 (0.4)		1 (0.5)		0 (0)		1
	+ Lung cancer			12 (5.0)		9 (4.4)		3 (8.3)		0.39
	+ Asthma			8 (3.3)		8 (3.9)		0 (0)		0.61
	+ Chronic tuberculosis			8 (3.3)		8 (3.9)		0 (0)		0.61
	+ Pneumoconiosis	only		5 (2.1)		4 (2.0)		1 (2.8)		0.56
		+ Asthma		1 (0.4)		1 (0.5)		0 (0)		1
	+ Bronchiectasis			2 (0.8)		2 (1.0)		0 (0)		1
	+ Aspergillosis			4 (1.7)		2 (1.0)		2 (5.6)		0.11
	+ Metastatic lung tumour			3 (1.3)		2 (1.0)		1 (2.8)		0.39
	+ BHD syndrome			2 (0.8)		2 (1.0)		0 (0)		1
ILD	ILD only			20 (8.4)		15 (7.4)		5 (13.9)		0.20
	+ Asthma			1 (0.4)		1 (0.5)		0 (0)		1
	+ Bronchiectasis	only		4 (1.7)		4 (2.0)		0 (0)		１
		+ NTM		1 (0.4)		0 (0)		1 (2.8)		0.15
Lung cancer			2 (0.8)		1 (0.5)		1 (2.8)		0.28
Asthma			5 (2.1)		5 (2.5)		0 (0)		1
Bronchiectasis	Bronchiectasis only			3 (1.3)		3 (1.5)		0 (0)		1
	+ NTM			3 (1.3)		3 (1.5)		0 (0)		1
	+ Pneumoconiosis			1 (0.4)		1 (0.5)		0 (0)		1
Chronic tuberculosis	Chronic tuberculosis only			2 (0.8)		1 (0.5)		1 (2.8)		0.28
	+ Aspergillosis			1 (0.4)		1 (0.5)		0 (0)		1
Pneumoconiosis			3 (1.3)		3 (1.5)		0 (0)		1
Concomitant pneumonia on admission			54 (22.6)		36 (17.7)		18 (50.0)		< 0.01

Data are presented as the number of patients (percentage of all patients). BHD syndrome: Birt–Hogg–Dubé syndrome, ILD: interstitial lung disease, NTM: nontuberculous mycobacteriosis.

Radiographic characteristics of pneumothoraces

Table 3 shows the radiographic characteristics of pneumothoraces. There was almost no difference between the disease on the left and right sides, and there was no significant association with in-hospital mortality. Regarding the size of pneumothorax, there was a poor association between the degree of collapse and in-hospital mortality for any criterion.

Table 3

Radiographic characteristics of pneumothorax
Characteristics		Total N = 239	In-hospital death		P-value
Characteristics		Total N = 239	- (N = 203)	+ (N = 36)
Side of pneumothorax	Left Right	104 (43.5) 135 (56.5)	90 (44.3) 113 (55.7)	14 (38.9) 22 (61.1)	0.59
Size of pneumothorax ACCP BTS The Japan Society for Pneumothorax and Cystic Lung Diseases	Small Large	167 (69.9) 72 (30.1)	139 (68.5) 64 (31.5)	28 (77.8) 8 (22.2)	0.33
	Small Large	135 (56.5) 104 (43.5)	114 (56.2) 89 (43.8)	21 (58.3) 15 (41.7)	0.86
	Mild Moderate Severe	59 (24.7) 126 (52.7) 54 (22.6)	50 (24.6) 103 (50.7) 50(24.6)	9 (25.0) 23 (63.9) 4 (11.1)	0.16
Data are presented as the number of patients (percentage of all patients).

Management of spontaneous pneumothorax

Table 4 shows the details of these treatments. Approximately 75% and 80% of patients with pneumothorax and those in the in-hospital death group respectively, received some treatment. For the management of pneumothorax, there was no significant difference between the two groups, except for zero surgical cases in the in-hospital death group. However, a treatment combining multiple methods was used more often in the survival group (15 patients vs. one patient).

Table 4

Management of pneumothorax
Characteristics	Total N = 239	In-hospital death		P-value
Characteristics	Total N = 239	- (N = 203)	+ (N = 36)	P-value
(a) Observation (b) Needle aspiration only (c) Chest tube drainage only (d) Chemical pleurodesis (e) Thoracographic fibrin glue sealing method only (f) Endobronchial Watanabe spigot placement only (g) Surgery (d) + (e) (d) + (f) (d) + (g) (d) + (e) + (f) (d) + (e) + (g) (d) + (e) + (f) + (g) (d) + (f) + (g) (e) + (f) (e) + (g) (e) + (f) + (g) (f) + (g)	58 (24.7) 6 (2.5) 111 (46.4) 20 (8.4) 1 (0.4) 1 (0.4) 26(10.9) 5 (2.1) 1 (0.4) 3(1.3) 4 (1.7) 0 (0) 1 (0.4) 0 (0) 0 (0) 1 (0.4) 0 (0) 1 (0.4)	51 (25.1) 5 (2.5) 89 (43.8) 15 (7.4) 1 (0.5) 1 (0.5) 26 (12.8) 4 (2.0) 1 (0.5) 3 (1.5) 4 (2.0) 0 (0) 1 (0.5) 0 (0) 0 (0) 1 (0) 0 (0) 1 (0.5)	7 (19.4) 1 (2.8) 22 (61.1) 5 (13.9) 0 (0) 0 (0) 0 (0) 1 (2.8) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)	0.53 1 0.07 0.20 1 1 0.02 0.56 1 1 1 - 1 - - 1 - 1
All of the other data are presented as the number of patients (percentage of all patients).

Survival

CCI, ADL, and concomitant pneumonia on admission were significantly different in the univariate analysis; therefore, Cox proportional hazards analysis was performed. Age and sex were not included in the study because the participants were ≥ 65 years, and pneumothorax was initially more common in men.

In the Cox proportional hazards analysis of ADL (p = 0.37), CCI (p = 0.01), and concomitant pneumonia on admission (p < 0.01), CCI and concomitant pneumonia on admission were independent predictors of in-hospital mortality.

Figure 1 shows the survival rate of the two groups of patients with pneumothorax, one group with concomitant pneumonia and the other without concomitant pneumonia on admission. A log-rank test was performed, and the p-value was < 0.01.

There was a significant difference in the survival rates between the groups with and without concomitant pneumonia on admission.

Figure 2 divides CCI into four groups and shows the survival rate of the patients in each group. We divided the CCI into low (0 points), medium (1–2 points), high (3–4 points), and very high (≥ 5 points) groups. A log-rank test was performed, with a p-value of 0.123.

Our study confirmed that older patients with pneumothorax, with or without underlying lung disease, who had concomitant pneumonia on admission should be treated with caution because of the high mortality rate. Although COPD and ILD are considered mortality risks for pneumothorax, this study suggests that concomitant pneumonia on admission may also be a mortality risk factor.

Our study is the second on pneumothorax in the older population in Japan, and we included 239 older patients, a more significant number than that in the previous study. Few studies have examined the mortality rate of spontaneous pneumothorax in the older population. The Japan Geriatrics Society and the Japan Gerontological Society have recently published a proposal to define older adults as ≥ 75 years⁹; however, internationally, older adults are defined as those aged ≥ 65 years. In this study, the definition of older patients was based on the World Health Organisation and United Nations classifications (patients aged ≥ 65 years).¹⁰ Since many patients have multiple rather than a single underlying pulmonary disease, we classified the patients more finely for investigation. In this study, 11.7% of patients had no underlying lung disease, indicating that primary pneumothorax can be recognised even in older patients. Emphysema was the most common underlying lung disease. The number of cases was small owing to the detailed classification; therefore, no significant differences were likely to be found. In this study, 22.6% of the patients had concomitant pneumonia on admission. A comparison of the survival and in-hospital death groups showed a significant difference (p < 0.01), suggesting that concomitant pneumonia on admission is a prognostic factor for in-hospital death.

The mortality rate among older spontaneous pneumothorax patients in our hospital was 15%, higher than that in the previous study. One reason is that our hospital has an emergency centre with 42 departments that handle tertiary care (where more severe illnesses are concentrated); hence, there are many severe cases with underlying diseases.

Few deaths were directly attributable to pneumothorax. In previous reports, the direct causes of death were COPD, pneumonia, heart disease, empyema, and sepsis.^4,11 Most of these were due to the progression of comorbidities. Our research suggests that patients with pneumothorax often die of comorbidities rather than pneumothorax itself.

In previous reports, the proportion of patients with pneumothorax and concomitant pneumonia on admission was as high as 11%,^4,12−14, but it reached 22.6% (54 cases) in our hospital. A total of 11% of the patients (28 cases) with PSP had only pneumothorax without an underlying pulmonary disease. On admission, the mortality rate was 33% (18/54) in patients with concomitant pneumonia. Only patients with pneumothorax without underlying lung disease were included among those with concomitant pneumonia on admission, and the mortality rate was as high as 29% (2/7 cases). Unlike in previous reports, patients with concomitant pneumonia on admission were more frequent with higher mortality rates, suggesting that concomitant pneumonia on admission may be a risk factor for mortality. The development of pneumonia in older patients is most likely due to their poor general health. Pneumonia in older patients is often caused by aspiration pneumonia due to poor swallowing function; however, bacterial pneumonia has also been recognised. Therefore, it is suggested that, even without any other underlying disease, older patients are likely to be in poor general condition and have fewer treatment choices for pneumothorax.

CCI was used to assess the severity of complications. Nineteen diseases were listed in the CCI, and higher scores were assigned to diseases with higher severity. A score was assigned to each disease, and each score was used to evaluate the severity of the complications.¹⁵ When the CCI was used to assess systemic comorbidities, mortality was higher in the group with higher scores. Systemic conditions likely affected the mortality in patients with pneumothorax; however, the log-rank test did not reveal a significant difference.

Pneumonia is more likely to occur in patients with systemic comorbidities, which may increase mortality rates.

As this study was a retrospective analysis at a single centre, it is necessary to confirm the results by a prospective study at multiple centres. The present study included patients aged ≥ 65 years with underlying diseases, limiting the possible confounding control of age and comorbidities. Further studies are needed to analyse the role of these potential confounders. In addition, pneumothorax is a recurrent disease. It is desirable to keep the patients under observation even after discharge from the hospital and observe them for the period until recurrence and death; however, the patients were observed only during hospitalisation. Unlike other countries, Japan does not have a unified medical record system, and without a visit to our hospital, physicians do not know how the patient turned out after discharge. Japan's medical and insurance systems are unique, and similar studies should be conducted in other countries.

Although COPD and ILDs are generally considered mortality risks for pneumothorax, the results suggest that concomitant pneumonia may also be a mortality risk factor for pneumothorax at admission.

ADL, activities of daily life; CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; PSP, primary spontaneous pneumothorax; SSP, secondary spontaneous pneumothorax.

Ethics approval and consent to participate

Ethics approval was granted by the Institutional Review Board of Iizuka Hospital (approval no. 21085).

Consent for publication

We consent for publication.

Availability of data and materials

The data that support the findings of this study are not publicly available because of privacy or ethical restrictions but are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Authors’ contributions

SN and KT had full access to all of the data in the study and were responsible for data integrity and data analysis accuracy. SN wrote the manuscript. YM, KU, TK, HO, YH, TS, and KT designed the study and interpreted the data.

Acknowledgements

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

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Mortality and Prognostic Factors for Spontaneous Pneumothorax in Older Adults: A Retrospective Study

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Background

Methods

Patients

Data and statistical analyses

Results

Patient characteristics

Cause of death

Underlying lung diseases

Radiographic characteristics of pneumothoraces

Management of spontaneous pneumothorax

Survival

Discussion

Conclusions

List Of Abbreviations

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