**COPD: Differential Diagnosis**

Maria Luisa Martinez Ortiz1 and Josep Morera1,2

*1Servei de Pneumologia, Hospital Universitario Germans Trias i Pujol 2CIBER Enfermedades Respiratorias-CIberes, Barcelona Spain* 

#### **1. Introduction**

Chronic obstructive pulmonary disease (COPD) is a high prevalent and impact socioeconomic disease. Although, cigarette smoking clearly fulfils all criteria to be classified as the etiology of COPD (Hill´s criteria), the latest version of GOLD does not include this concept clearly, therefore half century of main documents has been culminated and they has never mentioned in the definition, tobacco or cigarette smoking as cause of COPD. American Thoracic Society and European Respiratory Society (ATS / ERS) in the definition of COPD include the phrase "primarily caused by cigarette smoking". Nevertheless, the next page smoking changes from the category of "cause" to simply a "risk factor"; in fact, smoking is included in table 2 as a risk factor under the column of "exposures", together with socioeconomic status, environmental pollution, disease in childhood, or diet, among other. A reason for not to refer to cigarette smoking as aetiology is that only 15% of smokers are susceptible to COPD, a concept wrongly attributed to Fletcher. Although not all subjects exposed to cigarette smoking develop COPD does not preclude such exposure is the cause, just as not all people infected with *Mycobacterium tuberculosis* develop Tuberculosis, but there is no doubt about the etiologic role of mycobacteria. Another reason for nor establish smoking to the category of etiological factor in COPD is the existence of COPD in non-smokers.

Therefore, when the aetiology is not part of the definition of the disease, it is usually replaced by a clinical description and the definition based on clinical findings are very poor, so a new definition of COPD is needed to ensure a more valid an accurate way to manage this worldwide condition.

In the Table 1 shows some of the criteria that different societies, guidelines and organizations have been used to diagnose COPD.

Actually COPD is defined as postbronchodilator FEV1/FVC ratio < 70%. Threshold of FEV1/FVC <70% is agedependent and will probably lead to a significant degree of overdiagnosis of COPD in the elderly and underdiagnose young adults. GOLD guidelines recommend that using the lower limit of normal (LLN) values for FEV1/FVC is a way to minimize the misclassification. But use LLN we also overdiagnose healthy subjects. Although use post-bronchodilator FEV1/FVC ratio <0.70 simplify the diagnosis of COPD, some pulmonologists, ever more, consider a diagnosis of COPD can not be based only on spirometry parameters; it is important to include the presence of respiratory symptoms and exposure to risk factors.

COPD: Differential Diagnosis 107

Sjogren syndrome

Sarcoidosis

Chronic

Scleroderma HIV

Fabry disease Salla disease Amyloidosis

Others

percentage of susceptibility increases if others methods, better than simple spirometry, have

Although transfer of carbon monoxide (DLCO) and computed tomography (CT) with high resolution have demonstrated useful in early diagnosis of emphysema, they are underused. Disadvantages for Chest CT and other imaging techniques are expensive and irradiation

There are excellent reviews about alpha 1 antitrypsin deficiency (AATD). AATD is associated with impaired pulmonary antiproteasas defenses leading to unopposed protease activity. ATTD is the best model of COPD and emphysema. The clinical course is accelerated mainly by the smoking, but also by air pollution, and phenotype well-known. Some cases are diagnosed as asthma or bronchiectasis for clinical manifestations. Others may be diagnosed by hepatologists if the first manifestation is liver findings. In recent years, the characteristics in

Inflamatory bowel disease Wegener syndrome

Extrinsic allergic alveolitis

Birt-Hogg-Dubé syndrome

AIDS (Pneumocistis jiroveci) Placental transmogrification Paraneoplasic Pemphigus

Ligth chain deposition disease Relapsing polychondritis Tracheobronchomalacia

Ehler Danlos syndrome Tracheal stenosis Cord vocal paralysis Relapsing Polichondritis Traqueal neoplasia

Tracheobronchopathia achondropasia

Papilomatosis tracheobronchopathia multiple

Eosinophilic granuloma Lymphangioleiomyomatosis

Neurofibromatosis Tuberous sclerosis

COPD from smoking

COPD in non smokers Chronic Asthma (perennial)

Sequelae of tuberculosis

Marihuana smoking

 byssinosis pig farmers cabinetmakers

Digestive exposure

Bronchiolitis

Others

exposure.

(Sauropus androgynus)

 Bronchiolitis obliterans Diffuse panbronchiolitis

popcorn plant workers

Table 2. Causes of COPD syndrome

**3. Alpha-1-antitrypsin deficiency** 

been used to detect COPD.

Others

Occupational exposure coal miners pulmonary silicosis

Mitral stenosis Cardiac failure Anorexia nervosa Cystic fibrosis in adult Bronchiectasis

Aging

COPD from alpha 1 antitrypsin deficiency

Ambiental exposure (biomass smoke)

Endovenous exposure (heroin, cocain)

Obliterative bronchiolitis in microwave

bronchiolitis by rheumatoid arthritis

Sequelae accidental exposure (ammoniac)


ATS: American thoracic Society; BTS: British Thoracic Society; VC: Vital capacity; ECCS: European Community for Coal and Steel; ERS: European Respiratory Society; FEV1/ /FVC: ratio of forced expiratory volume in 1s to forced vital capacity; GOLD: Global Initiative for chronic obstructive lung disease; LLN: lower limit of normal (LLN); NICE: National Institute for health and clinical excellence; NLHEP: National Lung Health Education Program.

Table 1. Spirometry criteria to COPD in some guidelines Society

There are many diseases or processes that show a FEV1 / FVC post-bronchodilator < 70%, these processes constitute the great chapter of what we call "disease" COPD.

Although nosological or semantically, definition of COPD as a syndrome is questionable, recently the term has come to be considered by other authors. Table 2 outlines a long list (not exhaustive) of entities that may be associated with airflow obstruction syndrome or COPD. Most of them are common such as pneumoconiosis and other occupational diseases, Airway obstruction in pulmonary tuberculosis, some clinical forms of asthma, etc and other less common such as lymphangioleiomyomatosis, Bronchiolitis obliterans associated with consumption of Sauropus androgynus among others. This chapter will show a list of differential diagnosis, as complete as possible and some clues for the recognition of these processes vs COPD.
