Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disease caused by mutations in the folliculin gene, which encodes folliculin, a protein involved in several cellular processes, including growth and energy metabolism. BHD syndrome is characterized clinically by a triad of pulmonary cysts with increased risk of spontaneous pneumothorax; renal tumors, often with mixed histologic subtypes; and cutaneous fibrofolliculomas. Diagnosis is challenging and may require clinical examination, radiographic imaging, histopathological sampling, and genetic testing. Current management includes prompt pleurodesis for pneumothorax, serial imaging for renal tumor detection and surveillance, and screening relatives of index patients for BHD syndrome.

The lysosomal storage disorders, including acid sphingomyelinase deficiency (ASMD), Gaucher disease (GD), and Fabry disease (FD) are rare causes of pulmonary disease that should be considered when patients present with interstitial lung disease or chronic obstructive lung disease at a young age. Clues of underlying inherited disorders of metabolism include splenomegaly, hepatomegaly, thrombocytopenia for GD and ASMD, crazy paving pattern on chest computed tomography and low high-density lipoprotein cholesterol for ASMD, and obstructive lung disease in FD. Early institution of enzyme replacement therapies in these patients can result in organ preservation and improved outcomes.

Pulmonary alveolar microlithiasis is an ultrarare autosomal recessive lung disease caused by loss of a key pulmonary epithelial sodium phosphate cotransporter resulting in elevation of luminal phosphate and accumulation of calcium phosphate crystals in alveolar spaces. The disease is often discovered incidentally on routine chest films in asymptomatic individuals or through screening of families with a known history of pulmonary alveolar microlithiasis (PAM) and tends to progress slowly, often culminating in respiratory failure in late middle age. Current management is limited to supportive measures, with lung transplantation in end stage disease. Recent advances in the pathogenesis of PAM have suggested therapeutic approaches.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome due to a number of underlying disorders, leading to accumulation of surfactant proteins in the alveoli and respiratory insufficiency. The diagnostic workup is aimed at identifying the underlying cause. Detection of GM-CSF neutralizing autoantibodies in serum confirms autoimmune PAP and rules out other causes. Whole lung lavage can effectively restore the alveolar function, but not cure the disease. Inhalational GM-CSF has shown to improve the disease outcome in autoimmune PAP, while treating the underlying disease is crucial in secondary PAP. Targeted treatment is the future in PAP caused by gene mutations.

Interstitial lung diseases (ILDs) are a heterogenous group of disorders leading to progressive loss of lung function. A subset of ILD cases can be linked to specific single-gene causes. The available evidence suggests that known genetic etiologies should influence pharmacotherapy decisions for ILD patients, particularly when immunosuppression is considered. There is emerging consensus supporting screening of unaffected relatives of familial ILD patients to enhance early disease detection, while future studies exploring primary and secondary prevention of ILD in high-risk individuals offer hope of preventing the life-limited complications of these disorders.

The diagnosis of eosinophilic lung disease usually relies on characteristic clinical-imaging features and the demonstration of alveolar eosinophilia, while lung biopsy is generally not necessary. The etiology has practical implications, including interruption of a medicinal or illicit drugs, treatment of infections with parasites or fungi, or smoking cessation. The diagnosis of idiopathic eosinophilic pneumonia is considered only once all known causes of eosinophilia have been excluded, especially medications and infections. Treatment of eosinophilic lung diseases involves oral glucocorticoids in most cases and withdrawal of the offending agent when appropriate. Therapies that specifically target the interleukin-5 axis are increasing used.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder associated with oculocutaneous albinism, platelet storage pool disorder, and bleeding diathesis, and in certain subtypes, progressive fibrosing interstitial lung disease (ILD), inflammatory bowel disease, and immunodeficiency. Disease manifestations can be variable, and early recognition and diagnosis are needed to prevent complications. Progressive pulmonary fibrosis and respiratory failure are the leading cause of mortality in patients with HPS-1 and HPS-4. For these patients, surveillance for ILD, monitoring of lung function, treatment for pulmonary fibrosis, and early referral to lung transplantation centers are critical.

Amyloidosis and Light Chain Deposition Disease (LCDD) are disorders characterized by the deposition of abnormal proteins in tissues, leading to organ damage. Pulmonary involvement in amyloidosis can manifest as diffuse alveolar-septal amyloidosis, nodular or cystic pulmonary amyloidosis, or tracheobronchial involvement. The types of amyloidosis-immunoglobulin light chain), serum amyloid A, and transthyretin (ATTR)-affect the lungs differently, with ATTR being rare. LCDD, which primarily affects the kidneys, may also cause lung abnormalities, such as cystic or nodular disease. Both conditions are diagnosed through biopsy and imaging, with therapies targeting the underlying plasma cell or inflammatory disorders.

Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) and neuroendocrine hyperplasia of infancy (NEHI) are rare lung diseases occurring in adults and children, respectively and are characterized by the proliferation of pulmonary neuroendocrine cells. DIPNECH and NEHI are distinct clinical entities with varying clinical presentations and approaches to management. Airway obstruction, possibly caused by dysfunction in neuroendocrine signaling is common across both conditions. Greater understanding of the underlying pathogenesis is needed to develop future treatments in this area.

Lymphangioleiomyomatosis (LAM) is a progressive, female predominant, low-grade neoplasm that causes cystic remodeling of the lung. Diagnosing LAM involves a multifaceted approach, utilizing clinical assessments, imaging, and biomarkers. Management typically centers on pharmacologic treatment with the mechanistic target of rapamycin inhibitors, with additional strategies for symptomatic relief. Fueled by close collaboration between patients, scientists, and clinicians, discovery science in LAM has progressed rapidly resulting in the development of a blood-based diagnostic biomarker, Food and Drug Administration-approved therapy, worldwide network of clinics, and the discovery of multiple novel targets that are ripe for translation into new biomarkers and therapies.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease that affects young adults with exposure to cigarette smoke. PLCH granulomas infiltrate and destroy the wall of distal bronchioles. In adults, PLCH is usually isolated. The demonstration of constant activation of the mitogen-activated kinase pathway in all Langerhans cell histiocytosis (LCH) lesions has been a breakthrough in the understanding of the pathogenesis of LCH. Somatic mutations in RAS-RAF-MEK cascade (BRAF and other mutations) are present in over 85% of PLCH lesions. Currently, PLCH is best characterized as a myeloid neoplastic disorder with an inflammatory component, triggered by smoking.

Nitric oxide (NO) is an odorless gaseous molecule important for biological functions including regulation of vasodilation, smooth muscle relaxation, neurotransmission, platelet aggregation inhibition, and airway epithelial barrier function. It was first discovered in exhaled breath by Gustafsson and colleagues in 1991. However, interest in NO in respiratory medicine escalated following 2 successive independent reports, 1 showing elevated levels of NO in the exhaled breath of individuals with asthma and another demonstrating a decrease in exhaled NO in response to inhaled corticosteroid use. More than 2000 papers evaluate the use of the fraction of NO in exhaled breath, in lung disease.

Respiratory oscillometry measures impedance during tidal breathing and is a sensitive marker of smaller airway function. Recent consensus documents provide a framework for the clinician to incorporate this lung function test into routine clinical practice. Oscillometry has an established role in pediatric respiratory medicine. In adults, an abnormal oscillometry result relates to patient symptoms and clinically important outcomes especially in asthma and chronic obstructive pulmonary disease. There is increasing interest in the role of oscillometry when monitoring patients longitudinally including after lung transplantation, and a greater appreciation of intrabreath analysis and the detection of dynamic elastance.

Respiratory disease has a major impact on children's health, and objective measures of lung function are critical for the care and study of pediatric lung disease. Understanding lung development provides a conceptual framework for pulmonary function test (PFT) findings in children. Although the conventional age at which spirometry can be performed in children is 6 y, many children under this age can successfully perform spirometry. Other pediatric PFTs include oscillometry, multiple breath washout, measurement of specific airway resistance, and the interrupter technique. PFTs can also be performed in infants, but it requires a high degree of expertise and specialized equipment.

Disorders of the respiratory muscles (RM) are common, yet are often overlooked. Physical examination findings may suggest the presence of RM weakness but are nonspecific. Several tests of RM function are available, including measurements of upright and supine vital capacity, inspiratory and expiratory muscle pressures, sniff nasal inspiratory pressure, sniff esophageal and transdiaphragmatic pressures, and peak cough flow. These tests are widely available but are effort dependent. Electrodiagnostic studies, such as electromyography, electrical, or magnetic phrenic nerve stimulation, are effort independent but require more specialized equipment and staff. Imaging techniques such as ultrasound provide helpful complementary information about diaphragm function.

This article provides an overview of remote or home spirometry. It includes discussions about the types of devices available, their accuracy, and pitfalls. It also summarizes the data available for the use of home spirometry in specific pulmonary diseases such as lung transplant, cystic fibrosis, neuromuscular disease, and obstructive lung disease.

Interpretation of measured lung function values relies on reference equations to define the range of values that would be expected in otherwise healthy individuals. Reference equations for lung function can be interpreted in a way similar to pediatric growth charts and incorporate key anthropomorphic determinants of lung health: height, sex, and age. Race and ethnicity were previously included as a determinant of lung function through ethnic specific equations; however, this approach is no longer recommended because the potential harms outweigh the possible benefits. The clinical application of lung function results requires careful consideration of reference equations' derivations and their limitations.

This article is a high-level overview of strategies for successfully managing a pulmonary function laboratory with a particular focus on areas that are often neglected.

Therapeutic bronchoscopy is well established for palliative treatment of advanced malignancies, including for recanalization of malignant central airway obstruction. Although less common in clinical practice, bronchoscopic treatments (including thermal ablation) may also be considered for curative endobronchial treatment in several clinical scenarios including benign or occasionally low-grade purely endoluminal neoplasms. In this article, we highlight evidence for where endobronchial therapies for curative intent may be considered based on clinical experience over several decades. Although treatment of peripheral lung malignancies remains investigational at this time, advantages and disadvantages of several ablative techniques and potential immunostimulatory therapies are also discussed.