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Air Pollution and Chronic Cough in China
Andrew R. L. Medford, MD, FCCP Westbury-on-Trym, Bristol, England Affiliations: From the North Bristol Lung Centre, Southmead Hospital. Financial/nonfinancial disclosures: The author has reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Andrew R. L. Medford, MD, FCCP, North Bristol Lung Centre, Southmead Hospital, Westbury-on-Trym, Bristol, BS10 5NB, England; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0646
example, pulmonary hypertension associated with sarcoidosis may be a unifying diagnosis in some patients presenting with persistent MLAD.4 PET scanning and other studies may be suggestive in this setting,5 although sarcoidosis without pulmonary parenchymal findings is unlikely to be immediately life threatening, again justifying a period of observation prior to biopsy assessment if not regressing. There is a known frequent association of MLAD with interstitial lung disease,6 and, as such, diagnostic assessment without other clinical features of malignancy is likely unjustified. We suggest and agree with a cautious approach to MLAD associated with pulmonary hypertension of any cause, particularly if pretest suspicion for malignancy is low. Further prospective and observational work to refine a safe approach to MLAD in this setting is needed, as noted by Dr Medford. Teng Moua, MD David L. Levin, MD, PhD Jay H. Ryu, MD, FCCP Rochester, MN
References 1. Moua T, Levin DL, Carmona EM, Ryu JH. Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest. 2013;143(2):344-348. 2. Medford AR, Bennett JA, Free CM, Agrawal S. Mediastinal staging procedures in lung cancer: EBUS, TBNA and mediastinoscopy. Curr Opin Pulm Med. 2009;15(4):334-342. 3. Kumaran M, Benamore RE, Vaidhyanath R, et al. Ultrasound guided cytological aspiration of supraclavicular lymph nodes in patients with suspected lung cancer. Thorax. 2005;60(3): 229-233. 4. Medford AR, Bennett JA, Free CM, Agrawal S. Minimally invasive techniques for the diagnosis and staging of lung cancer. Clin Pulm Med. 2009;16(6):328-336.
Response
Affiliations: From the Division of Pulmonary and Critical Care (Drs Moua and Ryu), Department of Radiology (Dr Levin), Mayo Clinic Rochester. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Teng Moua, MD, Division of Pulmonary and Critical Care Medicine, Gonda 18 S, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0942
References To the Editor: We are grateful for the thoughtful commentary by Dr Medford relating to our recent article in CHEST.1 We agree that because procedural risk in patients with idiopathic pulmonary arterial hypertension (IPAH) is high, pretest suspicion for a more ominous diagnosis is warranted prior to invasive studies of associated mediastinal lymphadenopathy (MLAD). Specifically, exclusion of malignancy (lymphoma, lung primary, metastatic primary, and so forth) should be the only immediate justification for invasive assessment in this setting. Unfortunately, few studies have commented on MLAD associated with pulmonary hypertension. Our observed frequency of close to one in five patients with IPAH (18%) involved a selected cohort with both right-sided heart catheterization and chest CT scan for the purposes of correlating lymphadenopathy with severity of cardiac hemodynamics. This may underestimate the true prevalence of MLAD in all patients with IPAH. We did find a similar distribution and size of abnormal lymph nodes when compared with left-sided congestive adenopathy,2 and, although others have shown resolution or improvement in adenopathy following heart failure treatment,3 only one of nine patients with MLAD and follow-up CT scanning in our study had regression, despite receiving therapy. These specific findings from our study contribute to the clinical understanding of MLAD associated with pulmonary hypertension and may be applicable to MLAD with pulmonary hypertension from other causes. As Dr Medford noted, enlarged nodes of , 2 cm on short axis with known left- or right-sided heart disease may justify observation with directed heart failure management for 1 to 3 months prior to invasive assessment. This approach appears reasonable for MLAD and pulmonary hypertension from most causes. For
1. Moua T, Levin DL, Carmona EM, Ryu JH. Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest. 2013;143(2):344-348. 2. Ngom A, Dumont P, Diot P, Lemarié E. Benign mediastinal lymphadenopathy in congestive heart failure. Chest. 2001; 119(2):653-656. 3. Chabbert V, Canevet G, Baixas C, et al. Mediastinal lymphadenopathy in congestive heart failure: a sequential CT evaluation with clinical and echocardiographic correlations. Eur Radiol. 2004;14(5):881-889. 4. Handa T, Nagai S, Miki S, et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246-1252. 5. Prabhakar HB, Rabinowitz CB, Gibbons FK, O’Donnell WJ, Shepard JA, Aquino SL. Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT. AJR Am J Roentgenol. 2008; 190(suppl 3):S1-S6. 6. Souza CA, Müller NL, Lee KS, Johkoh T, Mitsuhiro H, Chong S. Idiopathic interstitial pneumonias: prevalence of mediastinal lymph node enlargement in 206 patients. AJR Am J Roentgenol. 2006;186(4):995-999.
Air Pollution and Chronic Cough in China To the Editor: In a recent issue of CHEST (March 2013), Lai et al1 demonstrated that cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, and atopic cough (AC) constituted the
362
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 07/08/2013
Correspondence
main causes of chronic cough across five regions in China, based on a prospective survey using a modified diagnostic algorithm. They also concluded that geography, seasonality, age, and sex were not related to the spectrum of chronic cough. We do agree with the authors’ viewpoint. However, of note, in developing countries like China one major concern with the environmental factors (haze) should be raised because indoor and outdoor pollutants can cause chronic cough; namely, exposure to pollutants, such as diesel exhaust, sulfur oxides, ozone, nitrogen oxides, and particulate matter, participates in the development of respiratory symptoms.2 Haze air pollution represents deterioration of the air quality, which is consistently associated with respiratory hospital admissions. Thurston et al3 indicated that haze contributed to 24% of respiratory admissions; a 30% increase in outpatient attendance due to haze-related conditions was also observed by Emmanuel4 after forest fires in Singapore. In China, haze has become a predominant problem confronted by 1.3 billion people in recent years, especially during the Chinese New Year, when fine particles and gaseous pollutants are released into the atmosphere after intensive displays of fireworks and firecrackers. It seems that the greater the air pollution the higher the prevalence of patients admitted to clinics with chronic cough as the chief complaint. The harmful effect of haze on the lungs may be related to the potential mechanism that particulates sedimentate in the lung, leading to pulmonary damnification and inflammation formation and subsequent reconditioning of the lung. Particulate matter camouflaged in the haze, as a recent value of air quality guidelines for the protection of health, was gradually recognized as a pollutant with significant impact on the pathogenesis of respiratory disease, with evidence of induction of oxidative stress both in vitro5 and in vivo.6 It would be helpful if the authors could investigate the association between particulate matter and chronic cough, to avoid bias introduced by this confounding factor. In addition, 64 cases, accounting for approximately 8.4% of the cohort reported by Lai et al,1 were diagnosed with unexplained cough, for which haze including particulate matter may be considered as the main cause, incorporating their role in the pathogenesy of chronic cough. Furthermore, subgroup analysis adjusted for daily environmental and meteorologic data across various regions will be appreciated, so as to clarify the causality relationship between environment and chronic cough. Although the four common causes of chronic cough in the article remain stable across the disparate regions (x2 5 1.782, P . .05) and are in the majority among the potential etiologic factors,1 the comparison of cough variant asthma (x2 5 15.902, P 5 .003), upper airway cough syndrome (x2 5 12.772, P 5 .012), and eosinophilic bronchitis (x2 5 12.326, P 5 .015) across five regions showed statistical significance, with an overall proportion of 68.4%.1 Therefore, it is inaccurate to suggest that no association between geography and the spectrum of chronic cough was observed in China. Wenjun Mao, MD Wei Xia, MD Jingyu Chen, MD Wuxi, China Affiliations: From the Department of Cardiothoracic Surgery (Drs Mao and Chen); and the Department of Intensive Care Unit (Dr Xia), Wuxi People’s Hospital, Nanjing Medical University. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Wenjun Mao, MD, Division of Cardiothoracic Surgery, Wuxi People’s Hospital, No. 299, Qing Yang Rd, Wuxi City, Jiangsu, China 214023; e-mail: [email protected]
© 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0611
References 1. Lai K, Chen R, Lin J, et al. A prospective, multicenter survey on causes of chronic cough in China. Chest. 2013;143(3): 613-620. 2. Groneberg-Kloft B, Kraus T, Mark Av, Wagner U, Fischer A. Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors. J Occup Med Toxicol. 2006;1:6. 3. Thurston GD, Ito K, Hayes CG, Bates DV, Lippmann M. Respiratory hospital admissions and summertime haze air pollution in Toronto, Ontario: consideration of the role of acid aerosols. Environ Res. 1994;65(2):271-290. 4. Emmanuel SC. Impact to lung health of haze from forest fires: the Singapore experience. Respirology. 2000;5(2):175-182. 5. Choi JH, Kim JS, Kim YC, Kim YS, Chung NH, Cho MH. Comparative study of PM2.5 - and PM10 - induced oxidative stress in rat lung epithelial cells. J Vet Sci. 2004;5(1):11-18. 6. Kim K, Park EY, Lee KH, Park JD, Kim YD, Hong YC. Differential oxidative stress response in young children and the elderly following exposure to PM(2.5). Environ Health Prev Med. 2009;14(1):60-66.
Response To the Editor: We thank Dr Mao and colleagues for their interest and comments regarding our recent article in CHEST.1 We agree that air pollution may be associated with cough. In a survey performed in six cities of northeastern China with heavy industrial air pollution, it was found that three air pollutants (total suspended particulates, SO2, NO2) significantly increased the prevalence of persistent cough in children (approximately 21%-28%).2 Another study in Hong Kong also showed that exposure to particulate matter in different geographic locations was associated with increased odds of having cough.3 It is reasonable to suppose that haze induces respiratory symptoms including cough. Air pollution is a common problem in China and is usually more serious in winter and spring. Therefore, the prevalence of cough may vary in different seasons because of air pollution, low temperature, and fireworks as mentioned by Dr Mao. However, our study was focused on the spectrum of causes of chronic cough in the specialist outpatient clinic but not the prevalence of chronic cough in the community. It is difficult to make a subgroup adjusted for air quality data across various regions to clarify its relationship with chronic cough in current cohort groups. A community survey with larger samples is needed in the future to confirm whether there are seasonal or regional differences on the prevalence of chronic cough related to air pollution in China. Dr Mao pointed out that haze should be the main cause of unexplained cough. In some patients with chronic cough, no cause is identified, leading to the diagnosis of idiopathic cough or unexplained cough, which is often associated with an increased response to tussive agents such as capsaicin. Common cold or influenza are often triggers of chronic cough (including the common causes and unexplained cough) in our experience. It is reported that air pollution exposure clearly exacerbates preexisting bronchial asthma,4 and sulfur dioxide exposure increases cough response and airway inflammation in guinea pigs.5 However, there is no study to identify that air pollutants are able to cause chronic cough or increase
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 07/08/2013
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363
example, pulmonary hypertension associated with sarcoidosis may be a unifying diagnosis in some patients presenting with persistent MLAD.4 PET scanning and other studies may be suggestive in this setting,5 although sarcoidosis without pulmonary parenchymal findings is unlikely to be immediately life threatening, again justifying a period of observation prior to biopsy assessment if not regressing. There is a known frequent association of MLAD with interstitial lung disease,6 and, as such, diagnostic assessment without other clinical features of malignancy is likely unjustified. We suggest and agree with a cautious approach to MLAD associated with pulmonary hypertension of any cause, particularly if pretest suspicion for malignancy is low. Further prospective and observational work to refine a safe approach to MLAD in this setting is needed, as noted by Dr Medford. Teng Moua, MD David L. Levin, MD, PhD Jay H. Ryu, MD, FCCP Rochester, MN
References 1. Moua T, Levin DL, Carmona EM, Ryu JH. Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest. 2013;143(2):344-348. 2. Medford AR, Bennett JA, Free CM, Agrawal S. Mediastinal staging procedures in lung cancer: EBUS, TBNA and mediastinoscopy. Curr Opin Pulm Med. 2009;15(4):334-342. 3. Kumaran M, Benamore RE, Vaidhyanath R, et al. Ultrasound guided cytological aspiration of supraclavicular lymph nodes in patients with suspected lung cancer. Thorax. 2005;60(3): 229-233. 4. Medford AR, Bennett JA, Free CM, Agrawal S. Minimally invasive techniques for the diagnosis and staging of lung cancer. Clin Pulm Med. 2009;16(6):328-336.
Response
Affiliations: From the Division of Pulmonary and Critical Care (Drs Moua and Ryu), Department of Radiology (Dr Levin), Mayo Clinic Rochester. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Teng Moua, MD, Division of Pulmonary and Critical Care Medicine, Gonda 18 S, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: [email protected] © 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0942
References To the Editor: We are grateful for the thoughtful commentary by Dr Medford relating to our recent article in CHEST.1 We agree that because procedural risk in patients with idiopathic pulmonary arterial hypertension (IPAH) is high, pretest suspicion for a more ominous diagnosis is warranted prior to invasive studies of associated mediastinal lymphadenopathy (MLAD). Specifically, exclusion of malignancy (lymphoma, lung primary, metastatic primary, and so forth) should be the only immediate justification for invasive assessment in this setting. Unfortunately, few studies have commented on MLAD associated with pulmonary hypertension. Our observed frequency of close to one in five patients with IPAH (18%) involved a selected cohort with both right-sided heart catheterization and chest CT scan for the purposes of correlating lymphadenopathy with severity of cardiac hemodynamics. This may underestimate the true prevalence of MLAD in all patients with IPAH. We did find a similar distribution and size of abnormal lymph nodes when compared with left-sided congestive adenopathy,2 and, although others have shown resolution or improvement in adenopathy following heart failure treatment,3 only one of nine patients with MLAD and follow-up CT scanning in our study had regression, despite receiving therapy. These specific findings from our study contribute to the clinical understanding of MLAD associated with pulmonary hypertension and may be applicable to MLAD with pulmonary hypertension from other causes. As Dr Medford noted, enlarged nodes of , 2 cm on short axis with known left- or right-sided heart disease may justify observation with directed heart failure management for 1 to 3 months prior to invasive assessment. This approach appears reasonable for MLAD and pulmonary hypertension from most causes. For
1. Moua T, Levin DL, Carmona EM, Ryu JH. Frequency of mediastinal lymphadenopathy in patients with idiopathic pulmonary arterial hypertension. Chest. 2013;143(2):344-348. 2. Ngom A, Dumont P, Diot P, Lemarié E. Benign mediastinal lymphadenopathy in congestive heart failure. Chest. 2001; 119(2):653-656. 3. Chabbert V, Canevet G, Baixas C, et al. Mediastinal lymphadenopathy in congestive heart failure: a sequential CT evaluation with clinical and echocardiographic correlations. Eur Radiol. 2004;14(5):881-889. 4. Handa T, Nagai S, Miki S, et al. Incidence of pulmonary hypertension and its clinical relevance in patients with sarcoidosis. Chest. 2006;129(5):1246-1252. 5. Prabhakar HB, Rabinowitz CB, Gibbons FK, O’Donnell WJ, Shepard JA, Aquino SL. Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT. AJR Am J Roentgenol. 2008; 190(suppl 3):S1-S6. 6. Souza CA, Müller NL, Lee KS, Johkoh T, Mitsuhiro H, Chong S. Idiopathic interstitial pneumonias: prevalence of mediastinal lymph node enlargement in 206 patients. AJR Am J Roentgenol. 2006;186(4):995-999.
Air Pollution and Chronic Cough in China To the Editor: In a recent issue of CHEST (March 2013), Lai et al1 demonstrated that cough variant asthma, upper airway cough syndrome, eosinophilic bronchitis, and atopic cough (AC) constituted the
362
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 07/08/2013
Correspondence
main causes of chronic cough across five regions in China, based on a prospective survey using a modified diagnostic algorithm. They also concluded that geography, seasonality, age, and sex were not related to the spectrum of chronic cough. We do agree with the authors’ viewpoint. However, of note, in developing countries like China one major concern with the environmental factors (haze) should be raised because indoor and outdoor pollutants can cause chronic cough; namely, exposure to pollutants, such as diesel exhaust, sulfur oxides, ozone, nitrogen oxides, and particulate matter, participates in the development of respiratory symptoms.2 Haze air pollution represents deterioration of the air quality, which is consistently associated with respiratory hospital admissions. Thurston et al3 indicated that haze contributed to 24% of respiratory admissions; a 30% increase in outpatient attendance due to haze-related conditions was also observed by Emmanuel4 after forest fires in Singapore. In China, haze has become a predominant problem confronted by 1.3 billion people in recent years, especially during the Chinese New Year, when fine particles and gaseous pollutants are released into the atmosphere after intensive displays of fireworks and firecrackers. It seems that the greater the air pollution the higher the prevalence of patients admitted to clinics with chronic cough as the chief complaint. The harmful effect of haze on the lungs may be related to the potential mechanism that particulates sedimentate in the lung, leading to pulmonary damnification and inflammation formation and subsequent reconditioning of the lung. Particulate matter camouflaged in the haze, as a recent value of air quality guidelines for the protection of health, was gradually recognized as a pollutant with significant impact on the pathogenesis of respiratory disease, with evidence of induction of oxidative stress both in vitro5 and in vivo.6 It would be helpful if the authors could investigate the association between particulate matter and chronic cough, to avoid bias introduced by this confounding factor. In addition, 64 cases, accounting for approximately 8.4% of the cohort reported by Lai et al,1 were diagnosed with unexplained cough, for which haze including particulate matter may be considered as the main cause, incorporating their role in the pathogenesy of chronic cough. Furthermore, subgroup analysis adjusted for daily environmental and meteorologic data across various regions will be appreciated, so as to clarify the causality relationship between environment and chronic cough. Although the four common causes of chronic cough in the article remain stable across the disparate regions (x2 5 1.782, P . .05) and are in the majority among the potential etiologic factors,1 the comparison of cough variant asthma (x2 5 15.902, P 5 .003), upper airway cough syndrome (x2 5 12.772, P 5 .012), and eosinophilic bronchitis (x2 5 12.326, P 5 .015) across five regions showed statistical significance, with an overall proportion of 68.4%.1 Therefore, it is inaccurate to suggest that no association between geography and the spectrum of chronic cough was observed in China. Wenjun Mao, MD Wei Xia, MD Jingyu Chen, MD Wuxi, China Affiliations: From the Department of Cardiothoracic Surgery (Drs Mao and Chen); and the Department of Intensive Care Unit (Dr Xia), Wuxi People’s Hospital, Nanjing Medical University. Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Correspondence to: Wenjun Mao, MD, Division of Cardiothoracic Surgery, Wuxi People’s Hospital, No. 299, Qing Yang Rd, Wuxi City, Jiangsu, China 214023; e-mail: [email protected]
© 2013 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-0611
References 1. Lai K, Chen R, Lin J, et al. A prospective, multicenter survey on causes of chronic cough in China. Chest. 2013;143(3): 613-620. 2. Groneberg-Kloft B, Kraus T, Mark Av, Wagner U, Fischer A. Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors. J Occup Med Toxicol. 2006;1:6. 3. Thurston GD, Ito K, Hayes CG, Bates DV, Lippmann M. Respiratory hospital admissions and summertime haze air pollution in Toronto, Ontario: consideration of the role of acid aerosols. Environ Res. 1994;65(2):271-290. 4. Emmanuel SC. Impact to lung health of haze from forest fires: the Singapore experience. Respirology. 2000;5(2):175-182. 5. Choi JH, Kim JS, Kim YC, Kim YS, Chung NH, Cho MH. Comparative study of PM2.5 - and PM10 - induced oxidative stress in rat lung epithelial cells. J Vet Sci. 2004;5(1):11-18. 6. Kim K, Park EY, Lee KH, Park JD, Kim YD, Hong YC. Differential oxidative stress response in young children and the elderly following exposure to PM(2.5). Environ Health Prev Med. 2009;14(1):60-66.
Response To the Editor: We thank Dr Mao and colleagues for their interest and comments regarding our recent article in CHEST.1 We agree that air pollution may be associated with cough. In a survey performed in six cities of northeastern China with heavy industrial air pollution, it was found that three air pollutants (total suspended particulates, SO2, NO2) significantly increased the prevalence of persistent cough in children (approximately 21%-28%).2 Another study in Hong Kong also showed that exposure to particulate matter in different geographic locations was associated with increased odds of having cough.3 It is reasonable to suppose that haze induces respiratory symptoms including cough. Air pollution is a common problem in China and is usually more serious in winter and spring. Therefore, the prevalence of cough may vary in different seasons because of air pollution, low temperature, and fireworks as mentioned by Dr Mao. However, our study was focused on the spectrum of causes of chronic cough in the specialist outpatient clinic but not the prevalence of chronic cough in the community. It is difficult to make a subgroup adjusted for air quality data across various regions to clarify its relationship with chronic cough in current cohort groups. A community survey with larger samples is needed in the future to confirm whether there are seasonal or regional differences on the prevalence of chronic cough related to air pollution in China. Dr Mao pointed out that haze should be the main cause of unexplained cough. In some patients with chronic cough, no cause is identified, leading to the diagnosis of idiopathic cough or unexplained cough, which is often associated with an increased response to tussive agents such as capsaicin. Common cold or influenza are often triggers of chronic cough (including the common causes and unexplained cough) in our experience. It is reported that air pollution exposure clearly exacerbates preexisting bronchial asthma,4 and sulfur dioxide exposure increases cough response and airway inflammation in guinea pigs.5 However, there is no study to identify that air pollutants are able to cause chronic cough or increase
journal.publications.chestnet.org
Downloaded From: http://journal.publications.chestnet.org/ by David Kinnison on 07/08/2013
CHEST / 144 / 1 / JULY 2013
363