Teofilo Lee-Chiong

Pulmonary Manifestations of Ankylosing Spondylitis

Ankylosing spondylitis, a chronic multisystem inflammatory disorder, can present with articular and extra-articular features. It can affect the tracheobronchial tree and the lung parenchyma, and respiratory complications include chest wall restriction, apical fibrobullous disease with or without secondary pulmonary superinfection, spontaneous pneumothorax, and obstructive sleep apnea. Ankylosing spondylitis is a common cause of pulmonary apical fibrocystic disease; early involvement may be unilateral or asymmetrical, but most cases eventually consist of bilateral apical fibrobullous lesions, many of which are progressive with coalescence of the nodules, formation of cysts and cavities, fibrosis, and bronchiectasis. Mycobacterial or fungal superinfection of the upper lobe cysts and cavities occurs commonly. Aspergillus fumigatus is the most common pathogen isolated, followed by various species of mycobacteria. Prognosis of patients with fibrobullous apical lesions is mainly determined by the presence, extent, and severity of superinfection. Pulmonary function test results are nonspecific and generally parallel the severity of parenchymal involvement. A restrictive ventilatory impairment can develop in patients with ankylosing spondylitis because of either fusion of the costovertebral joints and ankylosis of the thoracic spine or anterior chest wall involvement. Chest radiographic findings may mirror the severity of clinical involvement. Pulmonary parenchymal disease is typically progressive, and cyst formation, cavitation, and fibrosis are seen in advanced cases. No treatment has been shown to alter the clinical course of apical fibrobullous disease. Although several antiinflammatory agents, such as infliximab, etanercept, and adalimumab, are being used to treat ankylosing spondylitis, their effects on pulmonary manifestations are unclear.

Drug-induced pulmonary edema and acute respiratory distress syndrome.

Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

Medication Effects on Sleep and Breathing

Sleep respiration is regulated by circadian, endocrine, mechanical and chemical factors, and characterized by diminished ventilatory drive and changes in Pao2 and Paco2 thresholds. Hypoxemia and hypercapnia are more pronounced during rapid eye movement. Breathing is influenced by sleep stage and airway muscle tone. Patient factors include medical comorbidities and body habitus. Medications partially improve obstructive sleep apnea and stabilize periodic breathing at altitude. Potential adverse consequences of medications include precipitation or worsening of disorders. Risk factors for adverse medication effects include aging, medical disorders, and use of multiple medications that affect respiration.

Obesity and aging.

In this article, the combined effects of aging and obesity on the respiratory system are examined. Following a concise epidemiologic overview of the prevalence of obesity among older adults, the occurrence of prospective, often variable, health consequences related to this trend are considered as well as the observed effects of the association of both aging and obesity on respiratory anatomy, physiology, and diseases. Last, findings of research related to weight loss on respiratory function in obese older adults are summarized.

Circadian rhythm sleep disorders

Because there is insufficient cellular energy for organisms to perform their functions at the same constant rate and at the same time, all biologic processes show rhythmicity, each with its own unique frequency, amplitude, and phase. Optimal sleep and wakefulness requires proper timing and alignment of desired sleep-wake schedules and circadian rhythm-related periods of alertness. Persistent or recurrent mismatch between endogenous circadian rhythms and the conventional sleep-wake schedules of the environmental day can give rise to several circadian rhythm sleep disorders. Evaluation of suspected circadian rhythm sleep disorders requires proper monitoring of sleep diaries, often over several days to weeks. This article discusses the disorders of the circadian sleep-wake cycle and the therapeutic measures to correct the same.

Basic Biology of Sleep

Sleep can be defined as a complex reversible state characterized by behavioral quiescence, diminished responsiveness to external stimuli, and a stereotypical species-specific posture. Both components of sleep, non-rapid eye movement and rapid eye movement, are generated and maintained by central nervous system networks that use specific neurotransmitters located in specific areas of the brain. Widespread changes in physiologic processes occur during sleep, and these changes may influence the presentation and severity of specific medical disorders.

Drug-induced Pulmonary Disorders

The lung is a common target of drug toxicity. A variety of medications, including cancer chemotherapeutic drugs, anti-inflammatory medications, antimicrobial agents, cardiac drugs and anticonvulsants have been recognized as causative agents in the genesis of lung injury. As newer pharmacological agents are continuously being introduced into the therapeutic armamentarium, this list is expected to grow.

Sleep and breathing.

The sleep state is associated with significant changes in respiratory physiology, including ventilatory responses to hypoxia and hypercapnia, upper airway and intercostal muscle tone, and tidal volume and minute ventilation. These changes are further magnified in certain disease states, such as chronic obstructive pulmonary disease, restrictive respiratory disorders, neuromuscular conditions, and cardiac diseases. This article discusses the regulation of breathing during sleep in health and associated comorbid conditions.

Pulmonary Hemorrhage Syndromes

Diffuse pulmonary hemorrhage (DPH) is a syndrome defined by the clinical triad of hemoptysis, iron-deficiency anemia and transient diffuse acinar infiltrates on chest radiography [1–3]. Widespread damage of the alveolar-capillary lining leads to extensive hemorrhage from the pulmonary vasculature. DPH is caused by a heterogeneous group of disorders including Goodpasture’s syndrome, idiopathic pulmonary hemosiderosis, rapidly progressive glomerulonephritis, chemical-and drug-induced lung injury, coagulopathies, mitral stenosis and necrotizing pulmonary infections. This syndrome must be distinguished from localized alveolar hemorrhage with secondary spread of blood as seen with thromboembolism, chronic bronchitis, bronchiectasis, pneumonia and tumor [2].